Std10-Determination of Residual Solvent残留溶剂(中国药典CP 英文版)

<467> RESIDUAL SOLVENTS残留溶剂(Chapter under this new title—to become official July 1, 2008)（这个新名称下的通则----2008年7月1日起生效）(Current chapter title is <467> Organic Volatile Impurities)（当前通则名称是<467>有机挥发性杂质）INTRODUCTION介绍This general chapter applies to existing drug substances, excipients, and products. All substances and products are subject to relevant control of solvents likely to be present in a substance or product.本通则适用于现有原料药、辅助剂、成药。

所有原料药和成药均需对可能存在其中的溶剂进行控制。

Where the limits to be applied comply with those given below, tests for residual solvents are not generally mentioned in specific monographs because the solvents employed may vary from one manufacturer to another.在所适用的限度与下面所述相符的情况下，残留溶剂检测一般不在具体各论中提及，因为每个生产商所使用的溶剂可能都不相同。

The objective of this general chapter is to provide acceptable amounts of residual solvents in pharmaceuticals for the safety of the patient. The general chapter recommends the use of less toxic solvents and describes levels considered to be toxicologically acceptable for some residual solvents.本通则的目的是为了保障病人的安全，提供在药物中残留溶剂的可接受数量。

格拉布斯法—判断(2009-04-0716:38:20)标签：▲概述：一组测量数据中，如果个别数据偏离平均值很远，那么这个(这些)数据称作“可疑值”。

如果用统计方法—例如格拉布斯(Grubbs)法判断，能将“可疑值”从此组测量数据中剔除而参与平均值的计算，那么该“可疑值”就称作“(粗大误差)”。

本文就是介绍如何用格拉布斯法判断“可疑值”是否为“”。

▲测量数据：例如测量10次(n＝10)，获得以下数据：、、、、、、、、、。

▲排列数据：将上述测量数据按从小到大的顺序排列，得到、、、、、、、、、。

可以肯定，可疑值是最小值就是最大值。

▲计算平均值x-和标准差s：x-＝；标准差s＝。

计算时，必须将所有10个数据全部包含在内。

▲计算偏离值：平均值与最小值之差为－＝；最大值与平均值之差为－＝。

▲确定一个可疑值：比较起来，最大值与平均值之差大于平均值与最小值之差，因此认为最大值是可疑值。

▲计算G i值：G i＝(x i－x-)/s；其中i是可疑值的排列序号＝(x10－x-)/s＝－/＝。

由于x10－x-是残差，而s是标准差，——10号；因此G10因而可认为G是残差与标准差的比值。

下面要把计算值G i与格拉布斯表给出的10临界值G P(n)比较，如果计算的G i值大于表中的临界值G P(n)，则能判断该测量数据是，可以剔除。

但是要提醒，临界值G P(n)与两个参数有关：检出水平α(与置信概率P有关)和测量次数n(与自由度f有关)。

▲定检出水平α：如果要求严格，检出水平α可以定得小一些，例如定α＝，那么置信概率P＝1－α＝；如果要求严格，α可以定得大一些，例如定α＝，即P＝；通常定α＝，P＝。

▲查格拉布斯表获得临界值：根据选定的P值(此处为和测量次数n(此处为10)，查格拉布斯表，横竖相交得临界值G95(10)＝。

▲比较计算值G i和临界值G95(10)：G i＝，G95(10)＝，G i＞G95(10)。

▲判断是否为：因为G i＞G95(10)，可以判断测量值为，将它从10个测量数据中剔除。

Designation:D256–10Standard Test Methods forDetermining the Izod Pendulum Impact Resistance of Plastics1This standard is issued under thefixed designation D256;the number immediately following the designation indicates the year of original adoption or,in the case of revision,the year of last revision.A number in parentheses indicates the year of last reapproval.A superscript epsilon(´)indicates an editorial change since the last revision or reapproval.This standard has been approved for use by agencies of the Department of Defense.1.Scope*1.1These test methods cover the determination of the resistance of plastics to“standardized”(see Note1)pendulum-type hammers,mounted in“standardized”machines,in break-ing standard specimens with one pendulum swing(see Note2). The standard tests for these test methods require specimens made with a milled notch(see Note3).In Test Methods A,C, and D,the notch produces a stress concentration that increases the probability of a brittle,rather than a ductile,fracture.In Test Method E,the impact resistance is obtained by reversing the notched specimen180°in the clamping vise.The results of all test methods are reported in terms of energy absorbed per unit of specimen width or per unit of cross-sectional area under the notch.(See Note4.)N OTE1—The machines with their pendulum-type hammers have been “standardized”in that they must comply with certain requirements, including afixed height of hammer fall that results in a substantiallyfixed velocity of the hammer at the moment of impact.However,hammers of different initial energies(produced by varying their effective weights)are recommended for use with specimens of different impact resistance. Moreover,manufacturers of the equipment are permitted to use different lengths and constructions of pendulums with possible differences in pendulum rigidities resulting.(See Section5.)Be aware that other differences in machine design may exist.The specimens are“standard-ized”in that they are required to have onefixed length,onefixed depth, and one particular design of milled notch.The width of the specimens is permitted to vary between limits.N OTE2—Results generated using pendulums that utilize a load cell to record the impact force and thus impact energy,may not be equivalent to results that are generated using manually or digitally encoded testers that measure the energy remaining in the pendulum after impact.N OTE3—The notch in the Izod specimen serves to concentrate the stress,minimize plastic deformation,and direct the fracture to the part of the specimen behind the notch.Scatter in energy-to-break is thus reduced. However,because of differences in the elastic and viscoelastic properties of plastics,response to a given notch varies among materials.A measure of a plastic’s“notch sensitivity”may be obtained with Test Method D by comparing the energies to break specimens having different radii at the base of the notch.N OTE4—Caution must be exercised in interpreting the results of these standard test methods.The following testing parameters may affect test results significantly:Method of fabrication,including but not limited to processingtechnology,molding conditions,mold design,and thermaltreatments;Method of notching;Speed of notching tool;Design of notching apparatus;Quality of the notch;Time between notching and test;Test specimen thickness,Test specimen width under notch,andEnvironmental conditioning.1.2The values stated in SI units are to be regarded as standard.The values given in parentheses are for information only.1.3This standard does not purport to address all of the safety concerns,if any,associated with its use.It is the responsibility of the user of this standard to establish appro-priate safety and health practices and determine the applica-bility of regulatory limitations prior to use.N OTE5—These test methods resemble ISO180:1993in regard to title only.The contents are significantly different.2.Referenced Documents2.1ASTM Standards:2D618Practice for Conditioning Plastics for TestingD883Terminology Relating to PlasticsD3641Practice for Injection Molding Test Specimens of Thermoplastic Molding and Extrusion MaterialsD4066Classification System for Nylon Injection and Ex-trusion Materials(PA)D5947Test Methods for Physical Dimensions of Solid Plastics Specimens1These test methods are under the jurisdiction of ASTM Committee D20on Plastics and are the direct responsibility of Subcommittee D20.10on MechanicalProperties.Current edition approved May1,2010.Published June2010.Originally approved st previous edition approved in2006as D256-06a´1.DOI: 10.1520/D0256-10.2For referenced ASTM standards,visit the ASTM website,,or contact ASTM Customer Service at service@.For Annual Book of ASTM Standards volume information,refer to the standard’s Document Summary page on the ASTM website.*A Summary of Changes section appears at the end of this standard. Copyright©ASTM International,100Barr Harbor Drive,PO Box C700,West Conshohocken,PA19428-2959,United States.D6110Test Method for Determining the Charpy Impact Resistance of Notched Specimens of PlasticsE691Practice for Conducting an Interlaboratory Study to Determine the Precision of a Test Method2.2ISO Standard:ISO180:1993Plastics—Determination of Izod Impact Strength of Rigid Materials33.Terminology3.1Definitions—For definitions related to plastics see Terminology D883.3.2Definitions of Terms Specific to This Standard:3.2.1cantilever—a projecting beam clamped at only one end.3.2.2notch sensitivity—a measure of the variation of impact energy as a function of notch radius.4.Types of Tests4.1Four similar methods are presented in these test meth-ods.(See Note6.)All test methods use the same testing machine and specimen dimensions.There is no known means for correlating the results from the different test methods.N OTE6—Previous versions of this test method contained Test Method B for Charpy.It has been removed from this test method and has been published as D6110.4.1.1In Test Method A,the specimen is held as a vertical cantilever beam and is broken by a single swing of the pendulum.The line of initial contact is at afixed distance from the specimen clamp and from the centerline of the notch and on the same face as the notch.4.1.2Test Method C is similar to Test Method A,except for the addition of a procedure for determining the energy ex-pended in tossing a portion of the specimen.The value reported is called the“estimated net Izod impact resistance.”Test Method C is preferred over Test Method A for materials that have an Izod impact resistance of less than27J/m(0.5 ft·lbf/in.)under notch.(See Appendix X4for optional units.) The differences between Test Methods A and C become unimportant for materials that have an Izod impact resistance higher than this value.4.1.3Test Method D provides a measure of the notch sensitivity of a material.The stress-concentration at the notch increases with decreasing notch radius.4.1.3.1For a given system,greater stress concentration results in higher localized rates-of-strain.Since the effect of strain-rate on energy-to-break varies among materials,a mea-sure of this effect may be obtained by testing specimens with different notch radii.In the Izod-type test it has been demon-strated that the function,energy-to-break versus notch radius, is reasonably linear from a radius of0.03to2.5mm(0.001to 0.100in.),provided that all specimens have the same type of break.(See5.8and22.1.)4.1.3.2For the purpose of this test,the slope,b(see22.1), of the line between radii of0.25and1.0mm(0.010and0.040 in.)is used,unless tests with the1.0-mm radius give“non-break”results.In that case,0.25and0.50-mm(0.010and 0.020-in.)radii may be used.The effect of notch radius on the impact energy to break a specimen under the conditions of this test is measured by the value b.Materials with low values of b, whether high or low energy-to-break with the standard notch, are relatively insensitive to differences in notch radius;while the energy-to-break materials with high values of b is highly dependent on notch radius.The parameter b cannot be used in design calculations but may serve as a guide to the designer and in selection of materials.4.2Test Method E is similar to Test Method A,except that the specimen is reversed in the vise of the machine180°to the usual striking position,such that the striker of the apparatus impacts the specimen on the face opposite the notch.(See Fig. 1,Fig.2.)Test Method E is used to give an indication of the unnotched impact resistance of plastics;however,results ob-tained by the reversed notch method may not always agree with those obtained on a completely unnotched specimen.(See 28.1.)4,55.Significance and Use5.1Before proceeding with these test methods,reference should be made to the specification of the material being tested. Any test specimen preparation,conditioning,dimensions,and testing parameters covered in the materials specification shall take precedence over those mentioned in these test methods.If there is no material specification,then the default conditions apply.5.2The pendulum impact test indicates the energy to break standard test specimens of specified size under stipulated parameters of specimen mounting,notching,and pendulum velocity-at-impact.3Available from American National Standards Institute(ANSI),25W.43rd St., 4th Floor,New York,NY10036,.4Supporting data giving results of the interlaboratory tests are available from ASTM Headquarters.Request RR:D20-1021.5Supporting data giving results of the interlaboratory tests are available from ASTM Headquarters.RequestRR:D20-1026.FIG.1Relationship of Vise,Specimen,and Striking Edge to Each Other for Izod Test Methods A andC5.3The energy lost by the pendulum during the breakage of the specimen is the sum of the following:5.3.1Energy to initiate fracture of the specimen;5.3.2Energy to propagate the fracture across the specimen;5.3.3Energy to throw the free end (or ends)of the broken specimen (“toss correction”);5.3.4Energy to bend the specimen;5.3.5Energy to produce vibration in the pendulum arm;5.3.6Energy to produce vibration or horizontal movement of the machine frame or base;5.3.7Energy to overcome friction in the pendulum bearing and in the indicating mechanism,and to overcome windage (pendulum air drag);5.3.8Energy to indent or deform plastically the specimen at the line of impact;and5.3.9Energy to overcome the friction caused by the rubbing of the striker (or other part of the pendulum)over the face of the bent specimen.5.4For relatively brittle materials,for which fracture propa-gation energy is small in comparison with the fracture initiation energy,the indicated impact energy absorbed is,for all practical purposes,the sum of factors 5.3.1and 5.3.3.The toss correction (see 5.3.3)may represent a very large fraction of the total energy absorbed when testing relatively dense and brittle materials.Test Method C shall be used for materials that have an Izod impact resistance of less than 27J/m (0.5ft·lbf/in.).(See Appendix X4for optional units.)The toss correction obtained in Test Method C is only an approximation of the toss error,since the rotational and rectilinear velocities may not be the same during the re-toss of the specimen as for the original toss,and because stored stresses in the specimen may have been released as kinetic energy during the specimen fracture.5.5For tough,ductile,fiber filled,or cloth-laminated mate-rials,the fracture propagation energy (see 5.3.2)may be large compared to the fracture initiation energy (see 5.3.1).When testing these materials,factors (see 5.3.2,5.3.5,and 5.3.9)canbecome quite significant,even when the specimen is accurately machined and positioned and the machine is in good condition with adequate capacity.(See Note 7.)Bending (see 5.3.4)and indentation losses (see 5.3.8)may be appreciable when testing soft materials.N OTE 7—Although the frame and base of the machine should be sufficiently rigid and massive to handle the energies of tough specimens without motion or excessive vibration,the design must ensure that the center of percussion be at the center of strike.Locating the striker precisely at the center of percussion reduces vibration of the pendulum arm when used with brittle specimens.However,some losses due to pendulum arm vibration,the amount varying with the design of the pendulum,will occur with tough specimens,even when the striker is properly positioned.5.6In a well-designed machine of sufficient rigidity and mass,the losses due to factors 5.3.6and 5.3.7should be very small.Vibrational losses (see 5.3.6)can be quite large when wide specimens of tough materials are tested in machines of insufficient mass,not securely fastened to a heavy base.5.7With some materials,a critical width of specimen may be found below which specimens will appear ductile,as evidenced by considerable drawing or necking down in the region behind the notch and by a relatively high-energy absorption,and above which they will appear brittle as evidenced by little or no drawing down or necking and by a relatively low-energy absorption.Since these methods permit a variation in the width of the specimens,and since the width dictates,for many materials,whether a brittle,low-energy break or a ductile,high energy break will occur,it is necessary that the width be stated in the specification covering that material and that the width be reported along with the impact resistance.In view of the preceding,one should not make comparisons between data from specimens having widths that differ by more than a few mils.5.8The type of failure for each specimen shall be recorded as one of the four categories listed as follows:C =Complete Break —A break where the specimen separates into two or more pieces.H =Hinge Break —An incomplete break,such that one part of the specimen cannot support itself above the horizontal when the other part is held vertically (less than 90°included angle).P =Partial Break —An incomplete break that does not meet the definition for a hinge break but has frac-tured at least 90%of the distance between the vertex of the notch and the opposite side.NB =Non-Break —An incomplete break where the frac-ture extends less than 90%of the distance be-tween the vertex of the notch and the opposite side.For tough materials,the pendulum may not have the energy necessary to complete the breaking of the extreme fibers and toss the broken piece or pieces.Results obtained from “non-break”specimens shall be considered a departure from stan-dard and shall not be reported as a standard result.Impact resistance cannot be directly compared for any two materials that experience different types of failure as defined in the test method by this code.Averages reported must likewise be derived from specimens contained within a single failure category.This letter code shall suffix the reported impact identifying the types of failure associated with the reported value.If more than one type of failure is observed for asampleFIG.2Relationship of Vise,Specimen,and Striking Edge to EachOther for Test MethodEmaterial,then the report will indicate the average impact resistance for each type of failure,followed by the percent of the specimens failing in that manner and suffixed by the letter code.5.9The value of the impact methods lies mainly in the areas of quality control and materials specification.If two groups of specimens of supposedly the same material show significantly different energy absorptions,types of breaks,critical widths,or critical temperatures,it may be assumed that they were made of different materials or were exposed to different processing or conditioning environments.The fact that a material shows twice the energy absorption of another under these conditions of test does not indicate that this same relationship will exist under another set of test conditions.The order of toughness may even be reversed under different testing conditions.N OTE8—A documented discrepancy exists between manual and digital impact testers,primarily with thermoset materials,including phenolics, having an impact value of less than54J/m(1ft-lb/in.).Comparing data on the same material,tested on both manual and digital impact testers, may show the data from the digital tester to be significantly lower than data from a manual tester.In such cases a correlation study may be necessary to properly define the true relationship between the instruments.TEST METHOD A—CANTILEVER BEAM TEST6.Apparatus6.1The machine shall consist of a massive base on which is mounted a vise for holding the specimen and to which is connected,through a rigid frame and bearings,a pendulum-type hammer.(See 6.2.)The machine must also have a pendulum holding and releasing mechanism and a mechanism for indicating the breaking energy of the specimen.6.2A jig for positioning the specimen in the vise and graphs or tables to aid in the calculation of the correction for friction and windage also should be included.One type of machine is shown in Fig.3.One design of specimen-positioning jig is illustrated in Fig.4.Detailed requirements are given in subsequent paragraphs.General test methods for checking and calibrating the machine are given in Appendix X2.Additional instructions for adjusting a particular machine should be supplied by the manufacturer.6.3The pendulum shall consist of a single or multi-membered arm with a bearing on one end and a head, containing the striker,on the other.The arm must be suffi-ciently rigid to maintain the proper clearances and geometric relationships between the machine parts and the specimen and to minimize vibrational energy losses that are always includedin the measured impact resistance.Both simple and compound pendulum designs may comply with this test method.6.4The striker of the pendulum shall be hardened steel and shall be a cylindrical surface having a radius of curvature of 0.8060.20mm(0.03160.008in.)with its axis horizontal and perpendicular to the plane of swing of the pendulum.The line of contact of the striker shall be located at the center of percussion of the pendulum within62.54mm(60.100in.) (See Note9.)Those portions of the pendulum adjacent to the cylindrical striking edge shall be recessed or inclined at a suitable angle so that there will be no chance for other than this cylindrical surface coming in contact with the specimen during the break.N OTE9—The distance from the axis of support to the center of percussion may be determined experimentally from the period of small amplitude oscillations of the pendulum by means of the following equation:L5~g/4p2!p2FIG.3Cantilever Beam(Izod-Type)ImpactMachine FIG.4Jig for Positioning Specimen forClampingwhere:L=distance from the axis of support to the center of percussion,m or(ft),g=local gravitational acceleration(known to an accuracy of one part in one thousand),m/s2or(ft/s2),p= 3.1416(4p2=39.48),andp=period,s,of a single complete swing(to and fro)determined by averaging at least20consecutive and uninterrupted swings.Theangle of swing shall be less than5°each side of center.6.5The position of the pendulum holding and releasing mechanism shall be such that the vertical height of fall of the striker shall be61062mm(24.060.1in.).This will produce a velocity of the striker at the moment of impact of approxi-mately3.5m(11.4ft)/s.(See Note10.)The mechanism shall be so constructed and operated that it will release the pendulum without imparting acceleration or vibration to it.N OTE10—V5~2gh!0.5where:V=velocity of the striker at the moment of impact(m/s),g=local gravitational acceleration(m/s2),andh=vertical height of fall of the striker(m).This assumes no windage or friction.6.6The effective length of the pendulum shall be between 0.33and0.40m(12.8and16.0in.)so that the required elevation of the striker may be obtained by raising the pendulum to an angle between60and30°above the horizontal.6.7The machine shall be provided with a basic pendulum capable of delivering an energy of2.760.14J(2.0060.10 ft·lbf).This pendulum shall be used with all specimens that extract less than85%of this energy.Heavier pendulums shall be provided for specimens that require more energy to break. These may be separate interchangeable pendulums or one basic pendulum to which extra pairs of equal calibrated weights may be rigidly attached to opposite sides of the pendulum.It is imperative that the extra weights shall not significantly change the position of the center of percussion or the free-hanging rest point of the pendulum(that would consequently take the machine outside of the allowable calibration tolerances).A range of pendulums having energies from2.7to21.7J(2to16 ft·lbf)has been found to be sufficient for use with most plastic specimens and may be used with most machines.A series of pendulums such that each has twice the energy of the next will be found convenient.Each pendulum shall have an energy within60.5%of its nominal capacity.6.8A vise shall be provided for clamping the specimen rigidly in position so that the long axis of the specimen is vertical and at right angles to the top plane of the vise.(See Fig.1.)This top plane shall bisect the angle of the notch with a tolerance of0.12mm(0.005in.).Correct positioning of the specimen is generally done with a jig furnished with the machine.The top edges of thefixed and moveable jaws shall have a radius of0.2560.12mm(0.01060.005in.).For specimens whose thickness approaches the lower limiting value of3.00mm(0.118in.),means shall be provided to prevent the lower half of the specimen from moving during the clamping or testing operations(see Fig.4and Note11.)N OTE11—Some plastics are sensitive to clamping pressure;therefore,cooperating laboratories should agree upon some means of standardizing the clamping force.One method is using a torque wrench on the screw of the specimen vise.If the faces of the vise or specimen are notflat and parallel,a greater sensitivity to clamping pressure may be evident.See the calibration procedure in Appendix X2for adjustment and correction instructions for faulty instruments.6.9When the pendulum is free hanging,the striking surface shall come within0.2%of scale of touching the front face of a standard specimen.During an actual swing this element shall make initial contact with the specimen on a line22.0060.05 mm(0.8760.002in.)above the top surface of the vise. 6.10Means shall be provided for determining the energy expended by the pendulum in breaking the specimen.This is accomplished using either a pointer and dial mechanism or an electronic system consisting of a digital indicator and sensor (typically an encoder or resolver).In either case,the indicated breaking energy is determined by detecting the height of rise of the pendulum beyond the point of impact in terms of energy removed from that specific pendulum.Since the indicated energy must be corrected for pendulum-bearing friction, pointer friction,pointer inertia,and pendulum windage,in-structions for making these corrections are included in10.3and Annex A1and Annex A2.If the electronic display does not automatically correct for windage and friction,it shall be incumbent for the operator to determine the energy loss manually.(See Note12.)N OTE12—Many digital indicating systems automatically correct for windage and friction.The equipment manufacturer may be consulted for details concerning how this is performed,or if it is necessary to determine the means for manually calculating the energy loss due to windage and friction.6.11The vise,pendulum,and frame shall be sufficiently rigid to maintain correct alignment of the hammer and speci-men,both at the moment of impact and during the propagation of the fracture,and to minimize energy losses due to vibration. The base shall be sufficiently massive that the impact will not cause it to move.The machine shall be so designed,con-structed,and maintained that energy losses due to pendulum air drag(windage),friction in the pendulum bearings,and friction and inertia in the indicating mechanism are held to a minimum.6.12A check of the calibration of an impact machine is difficult to make under dynamic conditions.The basic param-eters are normally checked under static conditions;if the machine passes the static tests,then it is assumed to be accurate.The calibration procedure in Appendix X2should be used to establish the accuracy of the equipment.However,for some machine designs it might be necessary to change the recommended method of obtaining the required calibration measurements.Other methods of performing the required checks may be substituted,provided that they can be shown to result in an equivalent accuracy.Appendix X1also describes a dynamic test for checking certain features of the machine and specimen.6.13Micrometers—Apparatus for measurement of the width of the specimen shall comply with the requirements of Test Methods D5947.Apparatus for the measurement of the depth of plastic material remaining in the specimen under the notch shall comply with requirements of Test Methods D5947, provided however that the one anvil or presser foot shall beatapered blade conforming to the dimensions given in Fig.5.The opposing anvil or presser foot shall be flat and conforming to Test Methods D5947.7.Test Specimens7.1The test specimens shall conform to the dimensions and geometry of Fig.6,except as modified in accordance with 7.2,7.3,7.4,and 7.5.To ensure the correct contour and conditions of the specified notch,all specimens shall be notched as directed in Section 8.7.1.1Studies have shown that,for some materials,the location of the notch on the specimen and the length of the impacted end may have a slight effect on the measured impact resistance.Therefore,unless otherwise specified,care must be taken to ensure that the specimen conforms to the dimensions shown in Fig.6and that it is positioned as shown in Fig.1or Fig.2.7.2Molded specimens shall have a width between 3.0and 12.7mm (0.118and 0.500in.).Use the specimen width as specified in the material specification or as agreeduponN OTE 1—These views not to scale.N OTE 2—Micrometer to be satin-chrome finished with friction thimble.N OTE 3—Special anvil for micrometer caliper 0to 25.4mm range (50.8mm frame)(0to 1in.range (2-in.frame)).N OTE 4—Anvil to be oriented with respect to frame as shown.N OTE 5—Anvil and spindle to have hardened surfaces.N OTE 6—Range:0to 25.4mm (0to 1in.in thousandths of an inch).N OTE 7—Adjustment must be at zero when spindle and anvil are in contact.FIG.5Early (ca.1970)Version of a Notch-DepthMicrometerbetween the supplier and the customer.All specimens having one dimension less than 12.7mm (0.500in.)shall have the notch cut on the shorter side.Otherwise,all compression-molded specimens shall be notched on the side parallel to the direction of application of molding pressure.(See Fig.6.)N OTE 13—While subsection 7.5requires perpendicular pairs of plane parallel surfaces,the common practice has been to accept the non-parallel drafted surfaces formed when directly injection molding specimens for Izod ers must be aware that employing a trapezoidal section rather than a rectangular section may lead to data shifts and scatter.Unequal stress,created by clamping in the fracture region and dynamic twisting,caused by uneven striking of the specimen are prone to occur when the faces of the specimen are not parallel.Interlaboratory compari-sons must clearly spell out the specimen preparation conditions.7.2.1Extreme care must be used in handling specimens less than 6.35mm (0.250in.)wide.Such specimens must be accurately positioned and supported to prevent twist or lateral buckling during the test.Some materials,furthermore,are very sensitive to clamping pressure (see Note 11).7.2.2A critical investigation of the mechanics of impact testing has shown that tests made upon specimens under 6.35mm (0.250in.)wide absorb more energy due to crushing,bending,and twisting than do wider specimens.Therefore,specimens 6.35mm (0.250in.)or over in width are recom-mended.The responsibility for determining the minimumspecimen width shall be the investigator’s,with due reference to the specification for that material.7.2.3Material specification should be consulted for pre-ferred molding conditions.The type of mold and molding machine used and the flow behavior in the mold cavity will influence the impact resistance obtained.A specimen taken from one end of a molded plaque may give different results than a specimen taken from the other end.Cooperating laboratories should therefore agree on standard molds con-forming to the material specification.Practice D3641can be used as a guide for general molding tolerances,but refer to the material specification for specific molding conditions.7.2.4The impact resistance of a plastic material may be different if the notch is perpendicular to,rather than parallel to,the direction of molding.The same is true for specimens cut with or across the grain of an anisotropic sheet or plate.7.3For sheet materials,the specimens shall be cut from the sheet in both the lengthwise and crosswise directions unless otherwise specified.The width of the specimen shall be the thickness of the sheet if the sheet thickness is between 3.0and 12.7mm (0.118and 0.500in.).Sheet material thicker than 12.7mm shall be machined down to 12.7mm.Specimens with a 12.7-mm square cross section may be tested either edgewise or flatwise as cut from the sheet.When specimens are tested flatwise,the notch shall be made on the machined surface ifthemmin.A 10.1660.050.40060.002B 31.861.0 1.2560.04C 63.562.0 2.5060.08D 0.25R 60.050.010R 60.002E12.7060.200.50060.008FIG.6Dimensions of Izod-Type TestSpecimen。

第50卷第2期2023年北京化工大学学报(自然科学版)Journal of Beijing University of Chemical Technology (Natural Science)Vol.50,No.22023引用格式:陈晓楠,常玉,陈娇,等.一类离散神经系统中的混沌存在性[J].北京化工大学学报(自然科学版),2023,50(2):119-125.CHEN XiaoNan,CHANG Yu,CHEN Jiao,et al.Chaos in a discrete FitzHugh -Nagumo model[J].Journal of Beijing U⁃niversity of Chemical Technology (Natural Science),2023,50(2):119-125.一类离散神经系统中的混沌存在性陈晓楠　常　玉*　陈　娇　杨睿丰(北京化工大学数理学院,北京　100029)摘　要:研究了离散FitzHugh -Nagumo 神经系统的混沌现象㊂从理论上严格证明了在一定参数条件下系统存在Marotto 意义下的混沌,并通过数值计算模拟出该混沌吸引子,以及周期14轨㊁周期16轨等其他复杂动态㊂此外,通过Lyapunov 指数的计算对Marotto 混沌吸引子的存在性加以验证㊂关键词:离散FitzHugh -Nagumo 系统;Marotto 混沌;Lyapunov 指数中图分类号:O193 DOI :10.13543/j.bhxbzr.2023.02.015收稿日期:2022-01-05基金项目:国家自然科学基金(11771033)第一作者:女,1996年生,硕士生*通信联系人E⁃mail:changyu@引　言神经系统主导着生物体生理活动的调节,其功能主要通过神经元产生㊁处理和传递电信号来实现[1-2]㊂1952年,基于乌贼巨型轴突上电位变化的实验数据,Hodgkin 等[3]建立了一个四维非线性连续数学模型 Hodgkin -Huxley 模型(HH 模型),开启了对神经元电活动的数学研究㊂随后,FitzHugh [4]在保留系统主要动态的基础上,将HH 模型简化为二维系统;之后Nagumo 等[5]通过电路实验成功实现了该模型的动态,因此该模型也被称为FitzHugh -Nagumo 模型(FHN 模型)㊂由于系统的复杂性,针对FHN 模型的动态研究一直备受关注㊂Hayashi [6]给出了FHN 模型非平凡闭轨唯一性的充分条件㊂Rocşoreanu 等[7]证明了FHN 模型中saddle⁃node 分支㊁Hopf 分支以及Bogdanov -Takens分支的存在性㊂Jing 等[8]对FHN 模型应用Euler 方法得到离散FHN 系统,证明了该系统存在周期10轨㊁倍周期级联以及混沌等复杂动态㊂之后,Zhan 等[9]推广了一类离散FHN 模型,通过数值模拟分析了系统产生混沌的内外机制,以及延滞反馈项㊁高斯白色噪声项和磁场对激发神经元放电模式的影响㊂随着对该模型研究的深入,大量结果表明模型的动态对揭示现实中神经元放电活动的机制具有重要的参考价值㊂本文以文献[9]中的离散FHN 模型为研究对象,从理论上分析了系统中Marotto 混沌的存在性,得到了这类混沌存在的参数充分条件,并通过数值模拟展示了混沌吸引子㊁高周期解等复杂的非线性动态,这些结果丰富了对该模型的研究㊂1　离散FHN 模型1.1　模型描述考虑如下离散FHN 模型[9]f :æèçöø÷x y →x +(δx -x 33-y +)I y +δτ(ax +b -y æèççççöø÷÷÷÷)(1)式中,x 表示神经元膜电位;y 表示与膜电位恢复到静息电位过程有关的恢复变量;参数I (∈R )表示神经元接受的外界刺激强度或输入电流,其他系统参数a (>0)㊁b (∈R )㊁τ(>0)㊁δ(0<δ<1)的说明参见文献[9]㊂1.2　Marotto 意义下混沌的存在性在高维离散系统中存在的最典型的混沌吸引子是Marotto 混沌,这类混沌系统的动态十分复杂,如:该系统存在任意正整数周期的周期轨;同时拥有 scrambled”集,这是一个不包括周期点㊁不可数的㊁具有初值敏感性㊁没有渐近周期点的不变集㊂此类混沌的存在性完全由系统是否拥有某类特殊不动点即snap⁃back repeller 所决定[10-11]㊂本文将从理论上研究Marotto 意义下的混沌在系统(1)中的参数存在条件㊂应用离散动力系统的定性理论可得,当b =I ,0<a <1时,系统(1)存在一个不动点Z 0(x 0,y 0)=(3(1-a ),a3(1-a )+b )㊂此不动点Z 0是snap⁃back repeller 需要满足以下条件:①存在Z 0的一个邻域U Z 0,在此邻域中Z 0是expanding 不动点,即∀Z (x ,y )∈U Z 0,Z 所有特征值的模长均大于1;②U Z 0中存在一点Z *(x *,y *)≠Z 0,满足f M (Z *)=Z 0,|D f M (Z *)|≠0,M ∈N +㊂下面讨论Z 0(x 0,y 0)是snap⁃back repeller,即满足条件①㊁②的参数充分条件㊂引理1摇若23<a <1(2)2a -13a -2<τ<12-a -22a (1-a )(3)τ(2-3a )+12(1-a )<δ<1(4)则(ⅰ)存在点集U {=(x ,y )|x (∈1+1-2aττ,1+1-δaδ-)τ,y ∈}R ,该集合中任意点的特征值都是一对共轭复数,且模长大于1;(ⅱ)存在不动点Z 0(x 0,y 0)=(3(1-a ),a3(1-a )+b )的邻域U Z 0{=(x ,y )|(x -x 0)2r 2x 0+(y -y 0)2r 2y 0≤1,r x 0,r y 0∈R }+,满足UZ 0⊂U ㊂证明:(ⅰ)首先证明2a -13a -2<12-a -22a (1-a )㊂因为23<a <1,所以2a -13a -2=3a -2+1-a 3a -2=1+1-a3a -2>1㊂由(a (1-a )-(2a -1)2a (1-a ))㊃(a (1-a )+(2a -1)2a (1-a ))=(a (1-a ))2-((2a -1)2a (1-a ))2=-9a (1-a )(a -23()a -)13<0,可得a (1-a )-(2a -1)2a (1-a )<0㊂又因为(2-a -22a (1-a ))(2-a +22a (1-a ))=(2-a )2-(22a (1-a ))2=(9a -)232>0,故2-a -22a (1-a )>0,从而有2a -13a -2-12-a -22a (1-a )=2(a (1-a )-(2a -1)2a (1-a ))(3a -2)(2-a -22a (1-a ))<0㊂其次证明1+1-δa δ-τ>1+1-2aττ>0㊂显然τ+1>2τ>2aτ,故1+1-2aττ>0㊂由式(2)以及τ>2a -13a -2,可得τ-11-a >2a -13a -2-11-a=13a -2>1㊂又由2a -13a -2>1>δ,可知τ-11-a >δ,τ>δ,从而有1+1-δaδ-τ=δ(1-a )+1-τδ-τ=(1-a ()τ-11-a-)δτ-δ>0㊂因为2a -13a -2-1a =2(a -1)2a (3a -2)>0,所以2a -13a -2>1a ㊂由τ>2a -13a -2>1a ,可得aτ>1,从而2τ1-aτ<0㊂(注意到1+1-2aτ)τ(-1+1-δa δ-)τ=(1-aτ)(2δ-2τ1-a )ττ(δ-τ)<0,故1+1-2aττ<1+1-δaδ-τ㊂又因为1-δa δ-τ<0<1+2aττ,所以1+1-δaδ-τ<1+1+2aττ㊂综上可得,点集U {=(x ,y )|x ∈㊃021㊃北京化工大学学报(自然科学版) 2023年(1+1-2aττ,1+1-δaδ-)τ,y ∈}R 是存在的㊂任取Z (x ,y )∈U ,下面证明Z (x ,y )具有一对共轭复特征值,且模长大于1㊂易知系统(1)在点Z (x ,y )处的Jacobian 矩阵为J =1+δ(1-x 2)-δδa τ1-δæèççöø÷÷τ其特征方程为λ2+p (x )λ+q (x )=0,其中p (x )=-2+δτ-δ(1-x 2),q (x )=1-δτ+δ(1-x 2)-δ2τ(1-x 2)+δ2a τ,特征值为λ1,2=-p (x )±p 2(x )-4q (x )2㊂因为x (∈1+1-2aττ,1+1-δa δ-)τ,0<δ<τ,所以p 2(x )-4q (x )=δ(2x 2(-1+1-aτ))(τx 2(-1+1+2aτ))τ<0,q (x )-1=δ(δ-τ)(τx 2(-1+1-δa δ-))τ>0,从而有点Z (x ,y )的特征值为一对共轭复数λ1,2=-p (x )2±i4q (x )-p 2(x )2,且‖λ1,2‖=q (x )>1㊂(ⅱ)为选取适当的r x 0和r y 0,先证明1+1-2aττ<3(1-a )<1+1-δaδ-τ㊂因为a <1,τ(2-3a )+12(1-a )<δ,所以τ(2-3a )+1<2δ(1-a ),从而δ-τ+1-δa <3(1-a )(δ-τ)㊂又δ<τ,故3(1-a )<1+1-δa δ-τ(5)由a >23,0<τ<12-a -22a (1-a ),可得(3a -2)τ-2aτ+1<3a -22-a -22a (1-a )-2aτ+1<3a -22-a -243×13-2aτ+1=-2-2aτ<0,从而有1+1-2aττ-3(1-a )=(3a -2)τ-2aτ+1τ<0,即1+1-2aττ<3(1-a )(6)由式(5)㊁(6)可知1+1-2aττ<3(1-a )<1+1-δa δ-τ取0<r x 0{<min 1+1-δaδ-τ-3(1-a ),3(1-a )-1+1-2aτ}τ,r y 0∈R +,考虑不动点Z 0(x 0,y 0)=(3(1-a ),a 3(1-a )+b )的邻域U Z 0{=(x ,y )|(x -x 0)2r 2x 0+(y -y 0)2r 2y 0≤}1,任取点Z (x ,y )∈U Z 0,则其横坐标x ∈[x 0-r x 0,x 0+r x 0],显然[x 0-r x 0,x 0+r x 0](⊂1+1-2aττ,1+1-δaδ-)τ,故U Z 0⊂U ㊂命题得证㊂引理2　考虑不动点Z 0(x 0,y 0)=(3(1-a ),a3(1-a )+b ),及其邻域U Z 0{=(x ,y )|(x -x 0)2r 2x 0+(y -y 0)2r 2y 0≤1,r x 0=0.1,r y 0∈R }+,若式(2)~(4),以及δ≠τ1+aτ(7)30x 0+100(δ2x 0(-33a +1+4δ+4δaτ-))δ(㊃δ2aτ(τ-δ)2)(-1+1<3003a -2+1δ+δaτ-)δ(8)成立,则在邻域U Z 0中存在一点Z *(x *,y *),满足Z *≠Z 0,f 2(Z *)=Z 0,且|D f 2(Z *)|≠0㊂证明:设有点Z *(x *,y *),令Z 1(x 1,y 1)=f (Z *),f 2(Z *)=f (Z 1)=Z 0,即x 1=x *+(δx *-(x *)33-y *+)I y 1=y *+δτ(ax *-y *+b ìîíïïïï)(9)且㊃121㊃第2期 陈晓楠等:一类离散神经系统中的混沌存在性x 1+(δx 1-x 313-y 1+)I=xy 1+δτ(ax 1-y 1+b )=y {(10)易知方程组(10)的一组解为x 1+=-x 0(+33a +1+4δ+4δa τ-)δ2y 1+=y 0-δa (x 1+-x 0)τ-{δ(11)先证(x 1+,y 1+)≠(x 0,y 0)㊂由a >23,τ>δ可(得2x 0(-33a +1+4δ+4δaτ-))(δ-2x-(33a +1+4δ+4δa τ-))δ(=37a -3+4δ+4δa τ-)δ>(37×23-3+4δ+4δa τ-)δ(=5+121δ+δaτ-)δ>0,从而x 0-x 1+=2x 0(-33a +1+4δ+4δaτ-)δ≠0(12)将式(11)代入到方程组(10)可得(x *)3-3(δ1+δ+δ2a τ-)δx*+3(δ1-δ2aτ(τ-δ))2x 1++3aτ2(τ-δ)2x 0=0(13)y *=τ(τ-δ)y 0-δaτ(x 1+-x 0)-δ(ax *+b )(τ-δ)(τ-δ)2(14)为求方程(13)在[x 0-0.1,x 0+0.1]内的解x *,令x *=s +x 0,代入方程(13)可得g (s )≡s 3+3s 2x 0+3(s x 20-1-1δ-δaτ-)δ+3δ(×δ2aτ(τ-δ)2)-1(x 0-x 1+)=0(15)下面证明方程(15)在[-0.1,0.1]内有非零解,即g (s )有非零的零点㊂令g′(s )(=3s 2+2x 0s +x 20-1-1δ-δaδ-)τ=0,可得g (s )的两个驻点s 1,2=-x 0±1+1δ+δaτ-δ,其中s 1<s 2,显然当s ∈(s 1,s 2)时,g′(s )<0㊂因为τ>δ>0,所以1+1-δa δ-τ=1+δaτ-δ-1τ-δ<1+δa τ-δ+1δ,从而有s 2=1+1δ+δa τ-δ-3(1-a )>1+1-δaδ-τ-3(1-a )>0.1,且s 1=-s 2-23(1-a )<-0.1,故[-0.1,0.1]⊂(s 1,s 2)㊂因此当s ∈[-0.1,0.1]时,g′(s )<0,即g (s )在区间[-0.1,0.1]是单调递减函数㊂由式(7)及aτ>1,有δ2aτ-(τ-δ)2=(δ(1+aτ)-τ)(δ(aτ-1)+τ)≠0(16)由式(12)㊁(16)及τ>δ>0可得g (0)=3(x 0-x 1+)(δ2aτ-(τ-δ)2)δ(τ-δ)2≠0㊂且由式(8)㊁(12)可知,g (-0.1)g (0.1)(=30(1000x 0+100(x 0-x 1+)(δδ2aτ(τ-δ)2)))-12(-1(1000(3003a -2+1δ+δaτ-)δ))-12<0,根据零点定理得,∃s *∈(-0.1,0.1),g (s *)=0,又因g (0)≠0,故s *≠0㊂综上方程(13)有实根x *=x 0+s *∈(x 0-0.1,x 0+0.1),且x *≠x 0㊂取r y 0>|y *-y 0|,从而Z *(x *,y *)∈U Z 0,Z *≠Z 0,f 2(Z *)=Z 0㊂下证|D f 2(Z *)|≠0㊂|D f (Z *)|>0|D f (Z 1)|=δ2a τ(+1-δ)τ(1+δ(1-x21+))=(-1-δ)æèççτ3δ(1-a ()3a +1+4δ+4δa τ-)δ4+3δa2+2+öø÷÷δ-2δ2a τ<0故|D f 2(Z *)|=|D f (Z 1)‖D f (Z *)|≠0㊂命题得证㊂说明:引理2中的r x 0取值为0.1,事实上只要r x 0取充分小的正数,补充形如式(8)的条件,即可得相同的结论㊂综上所述,可得如下定理㊂定理　若系统参数a ㊁τ㊁δ满足引理1与引理2中的条件,则系统(1)的不动点Z 0(x 0,y 0)=(3(1-a ),a3(1-a )+b )是snap⁃back repel⁃ler,此时系统(1)是Marotto 混沌的,即存在:1)一个正整数N ,使得对于任一整数p ≥N ,f 有㊃221㊃北京化工大学学报(自然科学版) 2023年周期p 点㊂2)一个 scrambled set”,即一个不含周期点的不可数集S 满足(a)f [S ]⊂S ;(b)对于S 中任意不相同的两点X 和Y ,有lim k →∞sup ‖f k (X )-f k (Y )‖>0;(c)对于S 中任意点X ,以及f 的任意周期点Y ,有lim k →∞sup ‖f k (X )-f k (Y )‖>0㊂3)S 有一个不可数子集S 0,对于S 0中任意点X和Y ,有lim k →∞inf ‖f k (X )-f k (Y )‖=0㊂2　数值模拟本节取两组参数,通过数值计算,对Marotto 混沌吸引子及周期轨等复杂动态进行模拟㊂1)参数组1:b =I =1,a =0.9,τ=2.47,δ=0.992㊂系统(1)存在一个不动点㊂Z 0(x 0,y 0)=(0.54772255750517,1.492950301754653),其特征值为λ1,2=1.14639±0.24135i,‖λ1,2‖>1㊂此时参数满足引理1与引理2的条件:a =0.9>23τ(2-3a )+12(1-a )=-3.645<δ<11.143=2a -13a -2<τ<12-a -22a (1-a )=3.977δ≠τ1+aτ=0.9915830x 0+100(δ2x 0(-33a +1+4δ+4δaτ-))δ(×δ2aτ(τ-δ)2)(-1+1=3.488<3003a -2+1δ+δa τ-)δ=693.637引理1中的点集U 与Z 0的邻域U Z 0分别为U {=(x ,y )|x (∈1+1-2aττ,1+1-δa δ-)τ=(0.4445,0.9631),y ∈}R U Z 0{=(x ,y )|(x -x 0)20.01+(y -y 0)24≤}1显然U Z 0⊂U ㊂∀Z (x ,y )∈U Z 0,Z (x ,y )的特征方程为λ2+p (x )λ+q (x )=0,特征值为λ1,2=-p (x )±p 2(x )-4q (x )2,‖λ1,2‖=q (x )其中p 2(x )-4q (x )<p 2(x 0-0.1)-4q (x 0-0.1)=-0.00679<0,q (x )-1>q (x 0+0.1)-1=0.44606>0,即Z 的特征值为一对模长大于1的共轭复数㊂U Z 0中存在一点Z *(x *,y *)=(0.54652802940618,-0.462001800839748),Z 1(x 1,y 1)=f (Z *)=(2.485010260145796,0.32271318340719),f 2(Z *)=Z 0,且|D f 2(Z *)|=-2.9045㊂由定理可得Z 0是一个snap⁃back repel⁃ler,即系统(1)存在Marotto 混沌吸引子㊂选取不动点Z 0(x 0,y 0)=(0.54772255750517,1.492950301754653)的邻域U Z 0中的点(0.5477,1.493)为初始点,其相图见图1,这条轨道的Lya⁃punov 指数为{-0.24197,0.07866},即为Marotto混沌吸引子㊂图1　Marotto 混沌吸引子(δ=0.992)Fig.1　A Marotto chaotic attractor(δ=0.992)不同于前一组Z 0的邻域U Z 0中r x 0(=0.1)的取值,将r x 0设置为0.08,仍能证明在一定参数条件下系统是Marotto 意义下混沌的㊂2)参数组2:b =I =1,a =0.91,τ=2.4,δ=0.99㊂系统(1)存在不动点㊂Z 0(x 0,y 0)=(0.519615242270663,1.472849870466304),其特征值为λ1,2=1.1551±0.2334i,‖λ1,2‖>1㊂存在Z 0的邻域U Z 0{=(x ,y )|(x -x 0)2r 2x 0+(y -y 0)2r 2y 0≤1,r x 0=0.08,r y 0}=2.2任取Z (x ,y )∈U Z 0,因为p 2(x )-4q (x )<p 2(x 0-㊃321㊃第2期 陈晓楠等:一类离散神经系统中的混沌存在性0.08)-4q (x 0-0.08)=-0.01955<0,q (x )-1>q (x 0+0.08)=0.33163>0,所以Z (x ,y )有一对模长大于1的共轭复特征值-p (x )±i4q (x )-p 2(x )2,且其模长q (x )>1㊂U Z 0中存在点Z *(x *,y *)=(0.45525855258397,0.664929193926399),Z 1(x 1,y 1)=f (Z *)=(2.523106596180992,0.19274677774448),f 2(Z *)=Z 0,|D f 2(Z *)|=-3.0704≠0,由条件①㊁②得,Z 0(x 0,y 0)是snap⁃back repeller,系统(1)存在Marotto 混沌吸引子,这条轨道的Lyapunov 指数为{-0.18254,0.0651}㊂针对第一组参数值,在δ=0.992时系统(1)出现了Marotto 混沌吸引子㊂本文计算了参数δ∈(0.9,1)时,以不动点Z 0邻域中的点(0.5477,1.493)为初始点的轨道的最大Lyapunov 指数,如图2所示㊂很明显,系统在δ参数区间(0.988,1)内始终保持混沌状态㊂图2　最大Lyapunov 指数图Fig.2　The maximumLyapunov exponent diagram通过数值模拟计算,我们还发现系统存在高周期轨道,如周期16轨㊁周期14轨,如图3㊁4所示㊂图3　周期16轨(δ=0.9205)Fig.3　Period⁃16orbit(δ=0.9205)图4　周期14轨(δ=0.962)Fig.4　Period⁃14orbit(δ=0.962)3　结束语本文研究了一类离散FHN 神经系统的混沌现象,主要从理论上严格证明了该系统Marotto 意义下混沌的存在性㊂此外通过数值计算模拟出Marotto 混沌吸引子,同时还发现系统中存在周期14轨和周期16轨,这些复杂动态的发现丰富了对此系统的理解㊂参考文献:[1]　曲良辉,都琳,胡海威,等.电磁刺激对FHN 神经元系统的调控作用[J].动力学与控制学报,2020,18(1):40-48.QU L H,DU L,HU H W,et al.Regulation of electro⁃magnetic stimulation on FHN neuronal system[J].Jour⁃nal of Dynamics and Control,2020,18(1):40-48.(in Chinese)[2]　武春艳.神经元FitzHugh⁃Nagumo 模型的动力学分析[D].太原:太原理工大学,2015.WU C Y.Dynamical analysis of the neuronal FitzHugh⁃Nagumo model [D ].Taiyuan:Taiyuan University of Technolgy,2015.(in Chinese)[3]　HODGKIN A L,HUXLEY A F.A quantitative descrip⁃tion of membrane current and its application to conductionand excitation in nerve[J].Journal of Physiology,1952,117(4):500-544.[4]　FITZHUGH R.Impulses and physiological states in theo⁃retical models of nerve membrane[J].Biophysical Jour⁃nal,1961,1(6):445-466.[5]　NAGUMO J,ARIMOTO S,YOSHIZAWA S.An activepulse transmission line simulating nerve axon [J].Pro⁃ceedings of the IRE,1962,50(10):2061-2070.[6]　HAYASHI M.A note on the uniqueness of the closed or⁃bit of the FitzHugh -Nagumo system [J].Quarterly ofApplied Mathematics,2000,58(1):171-176.㊃421㊃北京化工大学学报(自然科学版) 2023年[7]　ROCŞOREANU C,GIURGIŢEANU N,GEORGESCUA.Connections between saddles for the FitzHugh -Nagu⁃mo system [J].International Journal of Bifurcation and Chaos,2001,11(2):533-540.[8]　JING Z J,JIA Z Y,CHANG Y.Chaos behavior in thediscrete FitzHugh nerve system [J].Science in China (Series A),2001,44(12):1571-1578.[9]　ZHAN F B,LIU S Q.A Hénon⁃like map inspired by thegeneralized discrete⁃time FitzHugh -Nagumo model[J].Nonlinear Dynamics,2019,97(10):2675-2691.[10]MAROTTO F R.Snap⁃back repellers imply chaos in R n [J].Journal of Mathematical Analysis and Applicaions,1978,63(1):199-223.[11]MAROTTO F R.On redefining a snap⁃back repeller[J].Chaos,Solitions and Fractals,2005,25(1):25-28.Chaos in a discrete FitzHugh -Nagumo modelCHEN XiaoNan　CHANG Yu *　CHEN Jiao　YANG RuiFeng(College of Mathematics and Physics,Beijing University of Chemical Technology,Beijing 100029,China)Abstract :Chaos phenomena in a discrete FitzHugh -Nagumo nervous model have been investigated.The existence of chaos in the sense of Marotto is analyzed theoretically.Numerical calculation studies for Lyapunov exponent dem⁃onstrate various complex dynamics,such as chaotic attractors,and period⁃14,and period⁃16orbits.Key words :discrete FitzHugh -Nagumo model;chaos in the sense of Marotto;Lyapunov exponent(责任编辑:吴万玲)㊃521㊃第2期 陈晓楠等:一类离散神经系统中的混沌存在性。

诚实考试吾心不虚 , 公平竞争方显实力, 考试失败尚有机会 , 考试舞弊前功尽弃。

上海财经大学《计量经济学 》课程考试卷（A ）闭卷课程代码 课程序号2008—2009 学年第 1 学期姓名 学号 班级一、单选题(每小题2分, 共计40分)1.如果模型中变量在10%的显著性水平下是显著的, 则（ D ）A. 该变量在5%的显著性水平下是也显著的B. 该变量在1%和5%的显著性水平下都是显著的C. 如果P 值为12%, 则该变量在15%的显著性水平下也是显著的 D 、 如果P 值为2%, 则该变量在5%的显著性水平下也是显著的 2.高斯－马尔可夫是( D )A.摇滚乐.B.足球运动.C.鲜美的菜.D.估计理论中的著名定理, 来自于著名的统计学家: Johan.Car.Friedric.Gauss 和Andre.Andreevic.Markov 。

3.以下关于工具变量的说法不正确的是（ B ）。

A.与随机干扰项不相关B. 与所替代的随机解释变量不相关C.与所替代的随机解释变量高度相关D.与模型中其他解释变量不相关4.在含有截距项的多元回归中, 校正的判定系数 与判定系数R2的关系有: （ B ） A.R2＜ B.R2＞ C.R2＝ D.R2与 的关系不能确定5.根据样本资料估计得出人均消费支出Y 对人均收入X 的回归模型为lnYi=2.00+0.75lnXi+ei, 这表明人均收入每增加1%, 人均消费支出将大约增加（ B ）A.0.2..B.0.75..C.2..D.7.5%6.在存在异方差的情况下, 普通最小二乘法（OLS ）估计量是（ B ） A.有偏的, 非有效的 B.无偏的, 非有效的 C.有偏的, 有效的 D.无偏的, 有效的7.已知模型的普通最小二乘法估计残差的一阶自相关系数为0, 则DW 统计量的近似值为（ C ）A.0B.1C.2D.48.在多元回归模型中, 若某个解释变量对其余解释变量回归后的判定系数接近1, 则表明原模型中存在（C）A.异方差性B.自相关C.多重共线性D.拟合优度低9.设某商品需求模型为: Yi＝β0＋β1Xi＋Ui, 其中Y是商品的需求量, X是商品的价格, 为了考虑全年12个月份季节变动的影响, 假设模型中引入了12个虚拟变量, 则会产生的问题是（D）A.异方差性B.自相关C.不完全的多重共线性D.完全的多重共线性10.下列表述不正确的是（D）A.尽管存在不完全的多重共线性, 普通最小二乘估计量仍然是最优线性无偏估计量B.双对数模型的R2可以与对数－线性模型的R2相比较, 但不能与线性－对数模型的R2相比较。

STD函数的内部计算公式各股票软件的标准差函数STD是不同的，⽽布林线的上下轨是以STD为基础计算出来的，所以使⽤布林线应⼩⼼。

以2008/3/28的上证综指为例，利⽤如下代码："收盘价3⽇STD:STD(CLOSE,3);"，三⽇收盘价分别是：3606.86，3580.15，3411.49，在飞狐交易师中显⽰的3⽇收盘价标准差是105.928，⼤智慧新⼀代中显⽰的是105.932，通达信中是86.49，同花顺中显⽰74.90。

⽤EXCEL中的函数STDEV计算的样本⽅差是105.9316，STDEVP计算总体⽅差是86.49。

可见⼤智慧和飞狐使⽤的算法是样本⽅差，⼆者数据基本⼀致，⼤智慧的更精确⼀点，通达信使⽤的是总体⽅差，同花顺就不知所谓了。

这⾥最关键的是要明⽩总体⽅差与样本⽅差的区别。

总体⽅差(population variance) ：如果这组数据本⾝便构成⼀个总体, 均差平⽅和除以数据中观察值的数⽬，称为总体⽅差。

如⼀组数据X1,X2,..., Xn：其平均值M=(X1+X2+...+Xn)/n ，总体⽅差为 [ (X1-M)^2+...(Xn-M)^2 ]/n 的平⽅根。

对于⽆限总体，N为⽆限⼤。

样本是由总体中任意抽取⽽形成的，样本的各种数量关系(包括平均值和⽅差)都是总体的相关数量的估计值。

数理统计学已经证明了，对于从总体中抽取的样本，⽤前⾯的总体⽅式公式计算出来的⽅差值来估计总体的⽅差总是偏⼩的。

样本⽅差有时也称为样本均⽅（mean square, 简记为MS），是总体⽅差的⽆偏估计，计算公式是[ (X1-M)^2+...(Xn-M)^2 ]/(n-1)的平⽅根，也就是说⽤(n-1)取代n作为分母。

为什么⽤n-1⽽不是n呢？这可以从⾃由度来解释。

这样看，X1,X2,...Xn是n个可以⾃由变化的样本，互不影响。

⽽X1-M, X2-M,...Xn-M是否也是n个⾃由变化的呢？不是……因为这n个统计量受到⼀个约束条件的影响就是之和等于0。

Analytical Procedures and Methods Validation for Drugsand BiologicsDRAFT GUIDANCEThis guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft document should be submitted within 90 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit electronic comments to . Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Registe r.For questions regarding this draft document contact (CDER) Lucinda Buhse 314-539-2134, or (CBER) Office of Communication, Outreach and Development at 800-835-4709 or 301-827-1800.U.S. Department of Health and Human ServicesFood and Drug AdministrationCenter for Drug Evaluation and Research (CDER)Center for Biologics Evaluation and Research (CBER)February 2014CMCAnalytical Procedures and Methods Validation for Drugsand BiologicsAdditional copies are available from:Office of CommunicationsDivision of Drug Information, WO51, Room 2201Center for Drug Evaluation and ResearchFood and Drug Administration10903 New Hampshire Ave., Silver Spring, MD 20993Phone: 301-796-3400; Fax: 301-847-8714druginfo@/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htmand/orOffice of Communication, Outreach andDevelopment, HFM-40Center for Biologics Evaluation and ResearchFood and Drug Administration1401 Rockville Pike, Rockville, MD 20852-1448ocod@/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm(Tel) 800-835-4709 or 301-827-1800U.S. Department of Health and Human ServicesFood and Drug AdministrationCenter for Drug Evaluation and Research (CDER)Center for Biologics Evaluation and Research (CBER)Febr uary 2014CMCTABLE OF CONTENTSI.INTRODUCTION (1)II.BACKGROUND (2)III.ANALYTICAL METHODS DEVELOPMENT (3)IV.CONTENT OF ANALYTICAL PROCEDURES (3)A.Principle/Scope (4)B.Apparatus/Equipment (4)C.Operating Parameters (4)D.Reagents/Standards (4)E.Sample Preparation (4)F.Standards Control Solution Preparation (5)G.Procedure (5)H.System Suitability (5)I.Calculations (5)J.Data Reporting (5)V.REFERENCE STANDARDS AND MATERIALS (6)VI.ANALYTICAL METHOD VALIDATION FOR NDA, ANDAs, BLAs, AND DMFs (6)A.Noncompendial Analytical Procedures (6)B.Validation Characteristics (7)pendial Analytical Procedures (8)VII.STATISTICAL ANALYSIS AND MODELS (8)A.Statistics (8)B.Models (8)VIII.LIFE CYCLE MANAGEMENT OF ANALYTICAL PROCEDURES (9)A.Revalidation (9)B.Analytical Method Comparability Studies (10)1.Alternative Analytical Procedures (10)2.Analytical Methods Transfer Studies (11)C.Reporting Postmarketing Changes to an Approved NDA, ANDA, or BLA (11)IX.FDA METHODS VERIFICATION (12)X.REFERENCES (12)Guidance for Industry11Analytical Procedures and Methods Validation for Drugs and2Biologics345This draft guidance, when finalized, will represent the Food and Drug Administration’s (FDA’s) current 6thinking on this topic. It does not create or confer any rights for or on any person and does not operate to 7bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of 8the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA9staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call 10the appropriate number listed on the title page of this guidance.11121314I. INTRODUCTION1516This revised draft guidance supersedes the 2000 draft guidance for industry on Analytical17Procedures and Methods Validation2,3 and, when finalized, will also replace the 1987 FDA18guidance for industry on Submitting Samples and Analytical Data for Methods Validation. It19provides recommendations on how you, the applicant, can submit analytical procedures4 and20methods validation data to support the documentation of the identity, strength, quality, purity,21and potency of drug substances and drug products.5It will help you assemble information and 22present data to support your analytical methodologies. The recommendations apply to drug23substances and drug products covered in new drug applications (NDAs), abbreviated new drug 24applications (ANDAs), biologics license applications (BLAs), and supplements to these25applications. The principles in this revised draft guidance also apply to drug substances and drug 26products covered in Type II drug master files (DMFs).2728This revised draft guidance complements the International Conference on Harmonisation (ICH) 29guidance Q2(R1)Validation of Analytical Procedures: Text and Methodology(Q2(R1)) for30developing and validating analytical methods.3132This revised draft guidance does not address investigational new drug application (IND) methods 33validation, but sponsors preparing INDs should consider the recommendations in this guidance.34For INDs, sufficient information is required at each phase of an investigation to ensure proper35identity, quality, purity, strength, and/or potency. The amount of information on analytical36procedures and methods validation will vary with the phase of the investigation.6 For general371 This guidance has been prepared by the Office of Pharmaceutical Science, in the Center for Drug Evaluation andResearch (CDER) and the Center for Biologics Evaluation and Research (CBER) at the Food and DrugAdministration.2 Sample submission is described in section IX, FDA Methods Verification.3 We update guidances periodically. To make sure you have the most recent version of a guidance, check the FDADrugs guidance Web page at/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.4Analytical procedure is interchangeable with a method or test procedure.5The terms drug substance and drug product, as used in this guidance, refer to human drugs and biologics.6 See 21 CFR 312.23(a)(7).guidance on analytical procedures and methods validation information to be submitted for phase 38one studies, sponsors should refer to the FDA guidance for industry on Content and Format of39Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including40Well-Characterized, Therapeutic, Biotechnology-Derived Products. General considerations for 41analytical procedures and method validation (e.g., bioassay) before conduct of phase three42studies are discussed in the FDA guidance for industry on IND Meetings for Human Drugs and 43Biologics, Chemistry, Manufacturing, and Controls Information.4445This revised draft guidance does not address specific method validation recommendations for46biological and immunochemical assays for characterization and quality control of many drug47substances and drug products. For example, some bioassays are based on animal challenge48models, and immunogenicity assessments or other immunoassays have unique features that49should be considered during development and validation.5051In addition, the need for revalidation of existing analytical methods may need to be considered 52when the manufacturing process changes during the product’s life cycle. For questions on53appropriate validation approaches for analytical procedures or submission of information not54addressed in this guidance, you should consult with the appropriate FDA product quality review 55staff.5657If you choose a different approach than those recommended in this revised draft guidance, we58encourage you to discuss the matter with the appropriate FDA product quality review staff before 59you submit your application.6061FDA’s guidance documents, including this guidance, do not establish legally enforceable62responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should 63be viewed only as recommendations, unless specific regulatory or statutory requirements are64cited. The use of the word should in Agency guidances means that something is suggested or65recommended, but not required.666768II.BACKGROUND6970Each NDA and ANDA must include the analytical procedures necessary to ensure the identity, 71strength, quality, purity, and potency of the drug substance and drug product.7 Each BLA must 72include a full description of the manufacturing methods, including analytical procedures that73demonstrate the manufactured product meets prescribed standards of identity, quality, safety,74purity, and potency.8 Data must be available to establish that the analytical procedures used in 75testing meet proper standards of accuracy and reliability and are suitable for their intended76purpose.9 For BLAs and their supplements, the analytical procedures and their validation are77submitted as part of license applications or supplements and are evaluated by FDA quality78review groups.79807 See 21 CFR 314.50(d)(1) and 314.94(a)(9)(i).8 See 21 CFR 601.2(a) and 601.2(c).9 See 21 CFR 211.165(e) and 211.194(a)(2).Analytical procedures and validation data should be submitted in the corresponding sections of 81the application in the ICH M2 eCTD: Electronic Common Technical Document Specification.108283When an analytical procedure is approved/licensed as part of the NDA, ANDA, or BLA, it84becomes the FDA approved analytical procedure for the approved product. This analytical85procedure may originate from FDA recognized sources (e.g., a compendial procedure from the 86United States Pharmacopeia/National Formulary (USP/NF)) or a validated procedure you87submitted that was determined to be acceptable by FDA. To apply an analytical method to a88different product, appropriate validation studies with the matrix of the new product should be89considered.909192III.ANALYTICAL METHODS DEVELOPMENT9394An analytical procedure is developed to test a defined characteristic of the drug substance or95drug product against established acceptance criteria for that characteristic. Early in the96development of a new analytical procedure, the choice of analytical instrumentation and97methodology should be selected based on the intended purpose and scope of the analytical98method. Parameters that may be evaluated during method development are specificity, linearity, 99limits of detection (LOD) and quantitation limits (LOQ), range, accuracy, and precision.100101During early stages of method development, the robustness of methods should be evaluated102because this characteristic can help you decide which method you will submit for approval.103Analytical procedures in the early stages of development are initially developed based on a104combination of mechanistic understanding of the basic methodology and prior experience.105Experimental data from early procedures can be used to guide further development. You should 106submit development data within the method validation section if they support the validation of 107the method.108109To fully understand the effect of changes in method parameters on an analytical procedure, you 110should adopt a systematic approach for method robustness study (e.g., a design of experiments 111with method parameters). You should begin with an initial risk assessment and follow with112multivariate experiments. Such approaches allow you to understand factorial parameter effects 113on method performance. Evaluation of a method’s performance may include analyses of114samples obtained from in-process manufacturing stages to the finished product. Knowledge115gained during these studies on the sources of method variation can help you assess the method 116performance.117118119IV.CONTENT OF ANALYTICAL PROCEDURES120121You should describe analytical procedures in sufficient detail to allow a competent analyst to 122reproduce the necessary conditions and obtain results within the proposed acceptance criteria. 123You should also describe aspects of the analytical procedures that require special attention. An 124analytical procedure may be referenced from FDA recognized sources (e.g., USP/NF,12510 See sections 3.2.S.4 Control of Drug Substance, 3.2.P.4 Control of Excipients, and 3.2.P.5 Control of DrugProduct.Association of Analytical Communities (AOAC) International)11 if the referenced analytical126procedure is not modified beyond what is allowed in the published method. You should provide 127in detail the procedures from other published sources. The following is a list of essential128information you should include for an analytical procedure:129130A.Principle/Scope131132A description of the basic principles of the analytical test/technology (separation, detection, etc.); 133target analyte(s) and sample(s) type (e.g., drug substance, drug product, impurities or compounds 134in biological fluids, etc.).135136B.Apparatus/Equipment137138All required qualified equipment and components (e.g., instrument type, detector, column type, 139dimensions, and alternative column, filter type, etc.).140141C.Operating Parameters142143Qualified optimal settings and ranges (allowed adjustments) critical to the analysis (e.g., flow144rate, components temperatures, run time, detector settings, gradient, head space sampler). A145drawing with experimental configuration and integration parameters may be used, as applicable. 146147D.Reagents/Standards148149The following should be listed:150151•Grade of chemical (e.g., USP/NF, American Chemical Society, High152Performance or Pressure Liquid Chromatography, or Gas153Chromatography and preservative free).154•Source (e.g., USP reference standard or qualified in-house reference material). 155•State (e.g., dried, undried, etc.) and concentration.156•Standard potencies (purity correction factors).157•Storage controls.158•Directions for safe use (as per current Safety Data Sheet).159•Validated or useable shelf life.160161New batches of biological reagents, such as monoclonal antibodies, polyclonal antisera, or cells, 162may need extensive qualification procedures included as part of the analytical procedure.163164E.Sample Preparation165166Procedures (e.g., extraction method, dilution or concentration, desalting procedures and mixing 167by sonication, shaking or sonication time, etc.) for the preparations for individual sample tests. 168A single preparation for qualitative and replicate preparations for quantitative tests with16911 See 21 CFR 211.194(a)(2).appropriate units of concentrations for working solutions (e.g., µg/ml or mg/ml) and information 170on stability of solutions and storage conditions.171172F.Standards Control Solution Preparation173174Procedures for the preparation and use of all standard and control solutions with appropriate175units of concentration and information on stability of standards and storage conditions,176including calibration standards, internal standards, system suitability standards, etc.177178G.Procedure179180A step-by-step description of the method (e.g., equilibration times, and scan/injection sequence 181with blanks, placeboes, samples, controls, sensitivity solution (for impurity method) and182standards to maintain validity of the system suitability during the span of analysis) and allowable 183operating ranges and adjustments if applicable.184185H.System Suitability186187Confirmatory test(s) procedures and parameters to ensure that the system (equipment,188electronics, and analytical operations and controls to be analyzed) will function correctly as an 189integrated system at the time of use. The system suitability acceptance criteria applied to190standards and controls, such as peak tailing, precision and resolution acceptance criteria, may be 191required as applicable. For system suitability of chromatographic systems, refer to CDER192reviewer guidance on Validation of Chromatographic Methods and USP General Chapter <621> 193Chromatography.194195I.Calculations196197The integration method and representative calculation formulas for data analysis (standards,198controls, samples) for tests based on label claim and specification (e.g., assay, specified and199unspecified impurities and relative response factors). This includes a description of any200mathematical transformations or formulas used in data analysis, along with a scientific201justification for any correction factors used.202203J.Data Reporting204205A presentation of numeric data that is consistent with instrumental capabilities and acceptance 206criteria. The method should indicate what format to use to report results (e.g., percentage label 207claim, weight/weight, and weight/volume etc.) with the specific number of significant figures 208needed. The American Society for Testing and Materials (ASTM) E29 describes a standard209practice for using significant digits in test data to determine conformance with specifications. For 210chromatographic methods, you should include retention times (RTs) for identification with211reference standard comparison basis, relative retention times (RRTs) (known and unknown212impurities) acceptable ranges and sample results reporting criteria.213214215V.REFERENCE STANDARDS AND MATERIALS216217Primary and secondary reference standards and materials are defined and discussed in the218following ICH guidances: Q6A Specifications: Test Procedures and Acceptance Criteria for 219New Drug Substances and New Drug Products: Chemical Substances (ICH Q6A), Q6B220Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological221Products, and Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical222Ingredients. For all standards, you should ensure the suitability for use. Reference standards for 223drug substances are particularly critical in validating specificity for an identity test. You should 224strictly follow storage, usage conditions, and handling instructions for reference standards to225avoid added impurities and inaccurate analysis. For biological products, you should include226information supporting any reference standards and materials that you intend to use in the BLA 227and in subsequent annual reports for subsequent reference standard qualifications. Information 228supporting reference standards and materials include qualification test protocols, reports, and 229certificates of analysis (including stability protocols and relevant known impurity profile230information, as applicable).231232Reference standards can often be obtained from USP and may also be available through the233European Pharmacopoeia, Japanese Pharmacopoeia, World Health Organization, or National 234Institute of Standards and Technology. Reference standards for a number of biological products 235are also available from CBER. For certain biological products marketed in the U.S., reference 236standards authorized by CBER must be used before the product can be released to the market.12 237Reference materials from other sources should be characterized by procedures including routine 238and beyond routine release testing as described in ICH Q6A. You should consider orthogonal 239methods. Additional testing could include attributes to determine the suitability of the reference 240material not necessarily captured by the drug substance or product release tests (e.g., more241extensive structural identity and orthogonal techniques for purity and impurities, biological242activity).243244For biological reference standards and materials, we recommend that you follow a two-tiered 245approach when qualifying new reference standards to help prevent drift in the quality attributes 246and provide a long-term link to clinical trial material. A two-tiered approach involves a247comparison of each new working reference standard with a primary reference standard so that it 248is linked to clinical trial material and the current manufacturing process.249250251VI.ANALYTICAL METHOD VALIDATION FOR NDA, ANDAs, BLAs, AND 252DMFs253254A.Noncompendial Analytical Procedures255256Analytical method validation is the process of demonstrating that an analytical procedure is257suitable for its intended purpose. The methodology and objective of the analytical procedures 258should be clearly defined and understood before initiating validation studies. This understanding 25912 See 21 CFR 610.20.is obtained from scientifically-based method development and optimization studies. Validation 260data must be generated under an protocol approved by the sponsor following current good261manufacturing practices with the description of methodology of each characteristic test and262predetermined and justified acceptance criteria, using qualified instrumentation operated under 263current good manufacturing practices conditions.13 Protocols for both drug substance and264product analytes or mixture of analytes in respective matrices should be developed and executed. 265266ICH Q2(R1) is considered the primary reference for recommendations and definitions on267validation characteristics for analytical procedures. The FDA Reviewer Guidance: Validation of 268Chromatographic Methods is available as well.269270B.Validation Characteristics271272Although not all of the validation characteristics are applicable for all types of tests, typical273validation characteristics are:274275•Specificity276•Linearity277•Accuracy278•Precision (repeatability, intermediate precision, and reproducibility)279•Range280•Quantitation limit281•Detection limit282283If a procedure is a validated quantitative analytical procedure that can detect changes in a quality 284attribute(s) of the drug substance and drug product during storage, it is considered a stability285indicating assay. To demonstrate specificity of a stability-indicating assay, a combination of286challenges should be performed. Some challenges include the use of samples spiked with target 287analytes and all known interferences; samples that have undergone various laboratory stress288conditions; and actual product samples (produced by the final manufacturing process) that are289either aged or have been stored under accelerated temperature and humidity conditions.290291As the holder of the NDA, ANDA, or BLA, you must:14 (1) submit the data used to establish292that the analytical procedures used in testing meet proper standards of accuracy and reliability, 293and (2) notify the FDA about each change in each condition established in an approved294application beyond the variations already provided for in the application, including changes to 295analytical procedures and other established controls.296297The submitted data should include the results from the robustness evaluation of the method,298which is typically conducted during method development or as part of a planned validation299study.1530013 See 21 CFR 211.165(e); 21 CFR 314.50 (d), and for biologics see 21 CFR 601.2(a), 601.2(c), and 601.12(a).14 For drugs see 21 CFR 314.50 (d), 314.70(d), and for biologics see 21 CFR 601.2(a), 601.2(c), and 601.12(a). For aBLA, as discussed below, you must obtain prior approval from FDA before implementing a change in analyticalmethods if those methods are specified in FDA regulations15 See section III and ICH Q2(R1).pendial Analytical Procedures302303The suitability of an analytical procedure (e.g., USP/NF, the AOAC International Book of304Methods, or other recognized standard references) should be verified under actual conditions of 305use.16 Compendial general chapters, which are complex and mention multiple steps and/or306address multiple techniques, should be rationalized for the intended use and verified. Information 307to demonstrate that USP/NF analytical procedures are suitable for the drug product or drug308substance should be included in the submission and generated under a verification protocol.309310The verification protocol should include, but is not limited to: (1) compendial methodology to 311be verified with predetermined acceptance criteria, and (2) details of the methodology (e.g.,312suitability of reagent(s), equipment, component(s), chromatographic conditions, column, detector 313type(s), sensitivity of detector signal response, system suitability, sample preparation and314stability). The procedure and extent of verification should dictate which validation characteristic 315tests should be included in the protocol (e.g., specificity, LOD, LOQ, precision, accuracy, etc.). 316Considerations that may influence what characteristic tests should be in the protocol may depend 317on situations such as whether specification limits are set tighter than compendial acceptance318criteria, or RT or RRT profiles are changing in chromatographic methods because of the319synthetic route of drug substance or differences in manufacturing process or matrix of drug320product. Robustness studies of compendial assays do not need to be included, if methods are 321followed without deviations.322323324VII.STATISTICAL ANALYSIS AND MODELS325326A.Statistics327328Statistical analysis of validation data can be used to evaluate validation characteristics against 329predetermined acceptance criteria. All statistical procedures and parameters used in the analysis 330of the data should be based on sound principles and appropriate for the intended evaluation.331Reportable statistics of linear regression analysis R (correlation coefficient), R square332(coefficient of determination), slope, least square, analysis of variance (ANOVA), confidence 333intervals, etc., should be provided with justification.For information on statistical techniques 334used in making comparisons, as well as other general information on the interpretation and335treatment of analytical data, appropriate literature or texts should be consulted.17336337B.Models338339Some analytical methods might use chemometric and/or multivariate models. When developing 340these models, you should include a statistically adequate number and range of samples for model 341development and comparable samples for model validation. Suitable software should be used for 342data analysis. Model parameters should be deliberately varied to test model robustness.34334416 See 21 CFR 211.194(a)(2) and USP General Chapter <1226> Verification of Compendial Procedures.17 See References section for examples including USP <1010> Analytical Data – Interpretation and Treatment.。

山东大学2021 2021年中级计量期末试卷山东大学2021-2021年中级计量期末试卷2022秋季硕士计量经济学期末考试一、判断题（）p值越大，就越应该拒绝原来的假设。

（）“以概率收敛”是“依分布收敛”的充分条件。

（）严格平稳过程一定是协方差平稳的；反之不然。

（）异方差或自相关的存在并不影响ols的一致性。

（）与white检验相比，BP检验可以检验任何形式的异方差。

（）缺少变量将不可避免地导致OLS估计不一致。

（）在arch/GARCH模型中，OLS估计仍然是蓝色的。

（）ADF试验为单侧右侧试验。

（）对于n个变量，最多可能有n-1个协整关系。

（）对于离散计数模型，应考虑probit或logit估计方法。

2、简短回答问题1、写出扰动项满足“严格外生性”的数学表达式。

2、写出迭代期望定律的表达式。

3.写出OLS平方和的分解公式。

为什么这个公式成立？4.陈述高斯-马尔可夫定律的假设和结论。

5.确保OLS估计一致性的最重要条件是什么？6、用于解决遗漏变量问题的“代理变量”应满足哪两个条件？7、列举可能导致扰动项与解释变量相关的三种情形。

8、一个有效的工具变量应满足哪两个条件？9、在什么情况下，gmm比2sls优越？10.当豪斯曼检验用于检验“内生解释变量”时，最初的假设是什么？11、断尾（truncated）回归、截取（censored）回归与偶然断尾（incidentaltruncation）回归的主要区别是什么？12.为什么随机实验数据通常比观测数据更有说服力？13、对于时间序列数据，在stata中使用什么命令（及句型）能得到“hac标准差”。

14、在stata中实现“似不相关回归”的命令（及句型）是什么？三、推导证明1、对于面板数据模型yit'?xit??zi'??ui??（,??n；t?1,??t），iti?1推导固定效应的“组内估计量”（withinestimator）。

2022秋季研究生计量经济学期末考试一、简答题（只要简洁地点出答案即可，无需推导或证明，每小题1分，共15分）1.对于经典线性回归模型y？十、最小二乘法的“正交性”是什么意思？2、直观来看，为什么2i？1宁？K是扰动项的方差？无偏估计，以及22e?i?1inn不是？3.统计数据的p值是多少？4、记似然函数为l(?;y)，请写出信息矩阵i(?)的定义式。

近红外光谱结合小波变换-随机森林法快速定量分析甲醇汽油中甲醇含量作者：李茂刚闫春华薛佳张天龙李华来源：《分析化学》2019年第12期摘;要;建立了一种基于近红外光谱（Near infrared spectroscopy，NIR）结合小波变换-随机森林（Wavelet transform-Random forest，WT-RF）的用于甲醇汽油中甲醇含量快速定量分析的方法。

采用傅里叶变换红外光谱仪采集54个甲醇汽油样品的光谱，并进行光谱解析;探究不同光谱预处理方法对样品NIR光谱的处理效果，重点探究基于不同小波基函数与小波分解层数的小波变换（Wavelet transform，WT）光谱预处理效果，并通过优化变量重要性阈值筛选随机森林RF校正模型的输入变量;基于优化后的参数及输入变量，构建了甲醇汽油NIR光谱的WT-RF模型。

为了进一步验证此模型的预测性能，将其与小波变换-偏最小二乘校正模型（Wavelet transform-Partial least squares，WT-PLS）和小波变换-最小二乘支持向量机校正模型（Wavelet transform-Least square support vector machine，WT-LSSVM）进行对比。

结果表明，WT-RF校正模型具有最佳的预测性能，其交叉验证决定系数（Coefficient of determination of cross-validation，R2cv）和均方根误差（Root mean square error of cross-validation，RMSECV）分别是0.9990和0.0044%，预测集决定系数（Coefficient of determination of prediction set，R2p）和均方根误差（Root mean square error of prediction set，RMSEP）分别为0.9885和0.0191%。

第二章之杨若古兰创作1绝对误差（Absolute error）：测量值与真值之差. 2绝对误差（Relative error）：绝对误差与真值的比值.3零碎误差（ Systematic error）（Determinate error可定误差）：由某种确定的缘由形成的误差.普通有固定的方向和大小，反复测量反复出现. 4偶然误差（ Accidental error，Random error随机误差）：由偶然身分惹起的误差.5精确度（Accuracy）：指测量值与真值接近的程度. 6精密度（Precision）：平等测量的各测量值之间互相接近的程度.7偏差（Deviation ）：单个测量值与测量平均值之差，可正可负.8平均偏差（Average deviation）：各单个偏差绝对值的平均值.9绝对平均偏差（Relative average deviation）：平均偏差与测量平均值的比值. （Coefficient of variation变异系数）10绝对尺度偏差（Relative standard deviation, RSD）：尺度偏差与测量平均值的比值.11无效数字（Significant figure）：在分析工作中实际上能测量到的数字.12反复性（Repeatability）：在同样操纵条件下，在较短时间间隔内，由同一分析人员对同一试样测定所得结果的接近程度.13两头精密度（Intermediate precision）：在同一实验室内，因为某些试验条件改变，对同一试样测定结果的接近程度. 14重现性（Reproducibility）：在分歧实验室之间，由分歧分析人员对同一试样测定结果的接近程度.15相信限（confidence limit）：先选定一个相信水平P，并在整体平均值的估计值x的两端各定出一个界限.16相信区间（confidence interval）：两个相信限之间的区间.17相信水平与明显性水平：指在某一t值时，测定值x落在μ±tS范围内的概率，称为相信水平（也称相信度或相信概率），用P暗示；测定值x落在μ±tS范围以外的概率（1－P），称为明显性水平，用α暗示.18 F检验：又称精密度明显性检验，通过比较两组数据的方差S2，以确定它们的精密度是否存在明显性差别19 t检验：也叫精确度明显性检验.次要用于检验两个分析结果是否存在明显的零碎误差，即判断少量实验数据的平均值与尺度试样尺度值之间是否存在明显性差别第三章滴定分析概论1滴定分析法（Titrimetric analysis）：将一种已知精确浓度的试剂溶液（尺度溶液），滴加到被测物资的溶液中，直到所加的试剂与被测物资按化学计量关系定量反应为止，然后根据所加试剂溶液的浓度和体积，计算出被测物资的量.2滴定（Titration）:进行滴定分析时，将被测物资溶液置于锥形瓶中，然后将尺度溶液（滴定剂）通过滴定管逐滴加到被测物资溶液中进行测定.3化学计量点（Stoichiometric point）：当加入的滴定剂的量与被测物资的量之间，正好符合化学反应式所暗示的计量关系时，称到达了化学计量点.4唆使剂（Indicator）：滴定分析中通过其色彩的变更来唆使化学计量点到达的试剂.普通有两种分歧色彩的存在型体. 5滴定起点(起点) （Titration end point(end point)）：滴定时，滴定至唆使剂改变色彩即停止滴定，这一点称为滴定起点.6滴定起点误差（Titration end point error）（titration error滴定误差TE）：因为滴定起点和化学计量点不符合惹起的绝对误差，属于方法误差，用TE%暗示.7滴定曲线(Titration curve)：以溶液中组分（被滴定组分或滴定剂）的浓度对加入的滴定剂体积作图.8滴定突跃（Abrupt change in titration curve）：滴定过程中，溶液浓度及其相干参数如Ph的突变.9突跃范围(Range of abrupt change in titration curve)：突跃所在的范围.唆使剂由一种型体色彩改变成另一型体色彩的溶液参数变更的范围.11理论变色点（Color transition point）：当两种型体浓度相等时，溶液呈现唆使剂的两头过渡色彩，这一点称为唆使剂的理论变色点.12滴定常数（Titration constant）：滴定反应的平衡常数，它反映滴定反应进行的完整程度.以Kt暗示.13直接滴定（Direct titration）：用尺度溶液直接滴定被测物资.14返滴定（Back titration）（residue titration剩余滴定）：先精确地加入过量尺度溶液，使与的待测物资或固体试样进行反应，待反应完整后，再用另一种尺度溶液滴定剩余的尺度溶液.15置换滴定(WordStrment titration)：用适当试剂与待测组分反应，使其定量地转换为另一种物资，而这类物资可用适当的尺度溶液滴定.16间接滴定（indirect titration）：不克不及与滴定剂直接反应的物资，有时可以通过另外的化学反应以滴定法间接滴定.17基准物资（Primary standard）：是用以直接配制尺度溶液或标定尺度溶液浓度的物资.18尺度溶液（Standard solution）：具有精确已知浓度的试剂溶液，在滴定分析中经常使用作滴定剂.19标定法（Standardization）：先配制成测验考试近似于所需浓度的溶液，然后用基准物资或曾经用基准物资标定过的尺度溶液来确定它的精确浓度.20物资的量浓度（Concentration）：单位体积尺度溶液中所含溶质的物资的量.21滴定度（Titer）：每毫升尺度溶液相当于被测物资的质量.22分析浓度（Analytical concentration）：溶液中该溶质各种平衡浓度的总和.23平衡浓度（ Equilibrium molarity）（species molarity型体浓度）：平衡形态时溶液中溶质各型体的浓度.24分布系数（Distribution fraction）：溶液中某型体的平衡浓度在溶质总浓度中所占的分数.25质量平衡（Mass balance）（material balance物料平衡）：在平衡形态下某一组分的分析浓度等于该组分各种型体的平衡浓度之和，这类关系称为质量平衡.26质量平衡方程（Mass balance equation）：质量平衡的数学表达式.27电荷平衡（Charge balance）：处于平衡形态的水溶液是电中性的，也就是溶液中荷正电质点所带正电荷的总数等于荷负电质点所带负电荷的总数，这类关系称为电荷平衡. 28质子平衡（Proton balance）：当酸碱反应达到平衡时，酸失去的质子数与碱得到的质子数相等，这类关系称为质子平衡.29朗伯比尔定律：光被透明介质接收的比例与入射光的强度有关；在光程上每等厚层介质接收不异比例值的光第四章酸碱滴定法1酸碱滴定法（Acid-base titration）：以质子转移反应为基础的滴定分析方法.2两性物资（Amphoteric substance）：在溶液中有两种离解方式，既可得到质子又可失去质子.3缓冲溶液（ Buffer solution）：一种能对溶液的酸度起感化的溶液.4酸碱唆使剂（Acid-base indicator）：是一类无机弱碱或弱酸，它们的共轭酸碱对具有分歧结构，因此呈现分歧的色彩.5非水滴定法（Nonaqueous titration）:是在非水溶剂中进行的滴定分析方法.6质子溶剂（Protonic solvent）：能给出质子或接受质子的溶剂.7酸性溶剂（Acid solvent）：是给出质子能力较强的溶剂. 8碱性溶剂（Basic solvent）：是接受质子能力较强的溶剂. 9两性溶剂（Amphoteric solvent）：是既易接受质子又易给出质子的溶剂，又称为中性溶剂，其酸碱性与水类似.10无质子溶剂（Aprotic solvent）：是分子中无转移性质子的溶剂.11均化效应（Leveling effect）：能将各种分歧强度的酸（或碱）均化到溶剂化质子（或溶剂阴离子）水平的效应.12区分效应（Differentiating effect）：能区分酸（或碱）强弱的效应.13区分性溶剂（Differentiating solvent）：具有区分效应的溶剂第五章配位滴定法1配位滴定法（Complex-formation titration）：以构成配位化合物反应为基础的滴定分析法.2螯合物（Chelate compound）：EDTA与金属离子构成多基配位体的配合物.3副反应系数（Side reaction coefficient）：定量地暗示副反应进行的程度.4酸效应（Acid effect）：因为H+的存在，在H+与Y之间发生副反应，使Y介入主反应能力降低的景象.5配位效应（Complex effect）：其他配位剂L与M发生副反应，使金属离子M与配位剂Y进行反应能力降低的景象.6条件波动常数（Conditional stability coefficient）：暗示在必定条件下，有副反应发生时主反应进行的程度.7金属唆使剂（Metal ion indicator）：一种能与金属离子生成有色配合物的无机染料显色剂，来唆使滴定过程中金属离子浓度的变更.8逐级波动常数和累积波动常数：逐级波动常数是指金属离子与其它配位剂L逐级构成MLn型配位化合物的各级构成常数.将逐级波动常数相乘，得到累积波动常数.9最高酸度：在配位滴定的条件下，溶液酸度的最高限制. 10最低酸度：金属离子发生水解的酸度.11封闭景象：某些金属离子与唆使剂生成极波动的配合物，过量的EDTA不克不及将其从MIn中夺取出来，乃至于在计量点附近唆使剂也不变色或变色不敏锐的景象.第六章氧化还原滴定1氧化还原滴定法（Oxidation-reduction titration）：以氧化还原反应为基础的一类滴定分析方法.2碘量法(Iodimetry)：利用I2的氧化性或I-的还原性进行氧化还原滴定的方法.3亚硝酸钠法（Sodium nitrite method)以亚硝酸钠为尺度溶液的氧化还原滴定法.4重氮化滴定法（Diazotization titration)：用亚硝酸钠液滴定芳伯胺类化合物的方法.5亚硝基化滴定法（Nitrosation titration)：用亚硝酸钠滴定芳仲胺类化合物的方法.6高锰酸钾法（Potassium permanganate method)：以高锰酸钾为尺度溶液的氧化还原滴定法.7重铬酸钾法（ Potassium dichromate method)：以重铬酸钾为尺度溶液的氧化还原滴定法.8条件电位（Conditional potential)：在必定条件下，氧化态与还原态的分析浓度均为1摩尔每升或它们的浓度比为1时的实际电位.9盐效应：溶液中盐类电解质对条件电位的影响.10酸效应：溶液酸度对条件电位的影响11本身唆使剂（Self indicator)：有些尺度溶液或被滴定物资本人具有很深的色彩，而滴定产品无色或色彩很浅，滴定时勿需另加唆使剂，它们本人色彩的变更就起着唆使剂的感化.12特殊唆使剂（Specific indicator)：本人无氧化还原性质，但能与氧化剂或还原剂感化的生特殊的色彩变更以唆使滴定起点.13外唆使剂（Outside indicator)：本人具有氧化还原性，能与尺度溶液或被测溶液发生氧化还原反应，故不克不及加入被测溶液中，只能在化学计量点附近，用玻棒蘸取被滴定的溶液在里面与其感化，根据色彩变更来判断滴定起点. 14氧化还原唆使剂（Oxidation-reduction indicator)：本人是弱氧化剂或弱还原剂，其氧化态和还原态具有分歧的色彩，在滴定过程中被氧化或还原后发生结构改变，惹起色彩变更来唆使起点.15不成逆唆使剂（Irreversible indicator)：在微过量尺度溶液存鄙人，可发生不成逆的色彩变更，从而唆使滴定起点的一类物资.第七章沉淀法和分量法1沉淀滴定法（Precipitation titration)：基于沉淀反应的滴定分析方法.2银量法（Argentimetry)：以银盐沉淀反应为基础的沉淀滴定方法.3分量分析法（Gravimetric analysis method)：通过称量物资的某种称量方式的质量来确定被测组分含量的一种定量分析方法.4沉淀法（Precipitation method)：利用沉淀反应将待测组分以难溶化合物方式沉淀上去，经过滤、洗濯、烘干或灼烧后，转化成具有确定构成的称量方式，称量并计算被测组分含量的分析方法.5挥发法（Volatilization method)：利用物资的挥发性质，通过加热或其他方法使被测组分从试样中挥发逸出.6萃取（Extraction method)：利用被测组分与其他组分互不混溶的两种溶剂平分配系数分歧，使被测组分从试样中定量转移至提取剂中而与其他组分分离.7沉淀方式（Precipitation form)：沉淀分量法中析出沉淀的化学构成.8称量方式(Weighing form：沉淀处理后具有固定构成、供最初称量的化学构成.9晶形沉淀Crystalline precipitate：颗粒较大，沉淀致密，易于滤过、洗濯.10无定形沉淀Amorphous precipitate：颗粒较小，沉淀疏松，不容易滤过、洗濯.11溶解度（Solubility)：平衡形态下所溶解的MA的总浓度. 12同离子效应（Common ion effect)：当沉淀反应达到平衡后，添加适量构晶离子的浓度使难溶盐溶解度降低的景象. 13酸效应（Acid effect)：溶液的酸度改变使难溶盐溶解度改变的景象.14配位效应（Complex effect)：当溶液中丰在能与金属离子生成可溶性配合物的配位剂时，使难溶盐溶解度增大的景象.15盐效应（Salt effect)：难溶盐溶解度随溶液中离子强度增大而添加的景象.16共沉淀（Coprecipitation)：当某种沉淀从溶液中析出时，溶液中共存的可溶性杂质也夹杂在该沉淀中一路析出的景象.17吸附共沉淀Adsorption coprecipitation：因为经常概况吸附惹起的共沉淀.18混晶共沉淀（Mixed crystal coprecipitation)：如果被吸附的杂质与沉淀具有不异的晶格、不异的电荷或离子半径，杂质离子可进入晶格排列惹起的共沉淀.19包埋共沉淀（Occlusion coprecipitation)：因为沉淀构成速度快，吸附在沉淀概况的杂质或母液来不及离开，被随后长大的沉淀所覆盖，包藏在沉淀内部惹起的共沉淀.20后沉淀（Postprecipitation)：在沉淀析出后，溶液中本来不克不及析出沉淀的组分，也在沉淀概况逐步沉积出来的景象. Aging陈化：将沉淀与母液一路放置的过程.21分量因数（Gravimetric factor)（换算因数）：是被测组分的摩尔质量与称量方式的摩尔质量之比，用F暗示.22均匀沉淀：利用化学反应使溶液中缓慢而均匀的发生沉淀剂，达到必定浓度时，发生颗粒大结构紧密易滤过洗濯的沉淀第八章电位法和永停滴定法1电化学分析法（electrochemical analysis）：是根据电化学道理和物资的电化学性质而建立起来的一类分析方法.2电解分析法(electrolytic analysis)：是根据电解道理建立起来的分析方法，包含电分量法，库仑法，及库仑滴定法.3电位分析法（potentiometry）：是以测定电池电动势为基础的分析方法，包含直接电位法和电位滴定法.4原电池(galvanic cell)：是一种将化学能改变成电能的安装.电极反应可自觉进行.5电解池（electrolytic cell）：是一种将电能改变成化学能的安装，外加电压才干电极反应. 6液接界：两溶液间的界面，亦称为液接界面(liquid junction boundary).7相界电位(phase boundary potential)：在金属与溶液两相界面上，因为带电质点的迁移构成了双电层，双电层间的电位差称为相界电位.8液接电位(liquid junction potential)：两个构成分歧或构成不异而浓度分歧的电解质溶液互相接触的界面所发生的电位差，称为液体接界电位，简称液接电位.9盐桥(salt bridge)：是沟通两个半电池、清除液接电位、坚持其电荷平衡、使反应顺利进行的一种安装.10唆使电极（indicator electrode）：是电极电位值随被测离子的活（浓）度变更而改变的一类电极.11参比电极（reference electrode）：在必定条件下，电位值已知且基本恒定的电极.12电位滴定法（potentiometric titration）：是根据在滴定过程中电池电动势的变更来确定滴定起点的一类滴定分析方法.13永停滴定法（dead-stop titration）：又称双电流或双安培滴定法，它是根据滴定过程中电流的变更确定滴定起点的方法，属于电流滴定法.14分歧错误称电位（asymmetry potential）：因为玻璃内外两概况的结果和功能不完整不异，使膜电位不等于0，这一电位差称为分歧错误称电位.15碱差：也称钠差，是指用Ph玻璃电极测定Ph>9的溶液时，测得的Ph小于真实值而发生的负误差.16酸差：是指用Ph玻璃电极测定Ph<1的溶液时，测得的Ph大于真实值而发生的正误差第九章光谱分析法概论1光学分析法（optical analysis）：是基于物资发射的电磁辐射或物资与辐射彼此感化后发生的辐射旌旗灯号或发生的旌旗灯号变更来测定物资的性质，含量和结构的一类仪器分析方法.2接收：是原子，分子或离子接收光子的能量，从基态跃迁到激发态的过程3发射：是物资从激发态跃迁回到基态，并以光的方式释放出能量的过程.4原子光谱法（atomic spectroscopy）：是以测定气态原子或离子外层或内层电子能级跃迁所发生的原子光谱为基础的成分分析方法.5分子光谱（molecular spectroscopy）：是由分子中电子能级、振动、和动弹能级的变更发生，表示方式为带光谱.次要分析方法有红外接收光谱法，紫外可见接收光谱法，分子荧光和磷光光谱法.6接收光谱：是物资接收呼应的辐射能而发生的光谱.7发射光谱：是指构成物资的原子、离子或分子受到辐射能等能量刺激跃迁到激发态后，又激发态回到基态时以辐射的方式释放能量，而发生的光谱.第十章紫外可见分光光度法1接收光谱（absorption spectrum）：又称接收曲线，是以波长为横坐标，以接收度A（或透光率T）为纵坐标所描绘的曲线.2接收峰：曲线上接收度最大的地方，所对应的波长称为对打接收波长.3谷：峰与峰之间吸光度最小的部位，该处的波长称最小波长.4肩峰（shoulder peak）：在一个接收峰旁边发生的一个曲折.5末端接收（end absorption）:只在图谱短波端呈现强接收而不成峰形的部分.6生色团（chromophore）（发色团）：是无机化合物分子结构中含有或跃迁的基团.即能在紫外可见光范围内发生接收的原子团.7助色团（auxochrome）：是指含有非键电子的杂原子饱和基团，当它们与生色团或饱和烃相连时，能使该生色团或饱和烃的接收峰向长波方向挪动，并使接收强度添加.8红移（red shift）（长移bathochromic shift)：是因为无机化合物结构改变，如发生共轭感化、引入助色团，和改变溶剂等，使接收峰向长波方向挪动的景象.9蓝（紫）移（blue shift）:亦称短移（hypsochromic shift）是化合物结构改变或受溶剂影响使接收峰向短波方向挪动的景象.10减色效应：因为化合物结构改变或其他缘由，使接收强度添加称减色效应或浓色效应（hyperchromic effect）.11减色效应：因为化合物结构改变或其他缘由，使接收强度减弱称减色效应或淡色效应（hypochromic effect）.12强带和弱带（strong band and weak band）:化合物的紫外可见接收光谱中，凡摩尔吸光系数大于104的接收峰称为强带，小与102的称弱带.13接收带（absorption band）:是说明接收峰在紫外可见光谱中的地位.14谱带宽度（band width）:光源为连续光谱时，采取单色器分离出来的光同时包含了所需波长的光和附近波长的光具有必定波长范围的光，这一宽度称谱带宽度.15透光率（transmittance ,T）：透射光强比入射光强.16吸光度（absorbance）：17摩尔吸光系数18百分吸光系数（比吸光系数）第十一章1荧光（fluorescence）：是物资分子接受光子能量被激发后，从激发态的最低振动能级返回基态时发射出的光.2荧光分析法（fluoromety）：是根据物资的荧光谱线地位及其强度进行物资鉴定和含量测定的方法.3三重态或三线态（triplet state）：当两个电子自旋方向不异时，自旋量子数都为1/2，其总自旋量子数s=1.电子能级的多重性用M=2s+1=3，即自旋方向不异的电子能级多重性为3，此时分子所处的电子能态称为三重态或三线态，用T 暗示.4单重态或单线态（single state）：在给定轨道中的两个电子，肯定以相反方向自旋，自旋量子数分别为1/2和-1/2，其总自旋量子数s=0.电子能级的多重性用M=2s+1=1，即自旋方向相反的电子能级多重性为1.此时分子所处的电子能态称为单重态或单线态，用S暗示.5振动弛豫（vibrational relaxation）：处于激发态各振动能级的分子通过与溶剂分子的碰撞而将部分振动能量传递给溶剂分子，其电子则返回到同一电子激发态的最低振动能级的过程激发态的最低振动能级的过程.6内部能量转换（internal conversion）：简称内转换.是当两个电子激发态之间的能量相差较小乃至其振动能级有堆叠时，受激分子常由高电子能级以无辐射方式转移至低振动能级的过程.7内部能量转换（external conversion）：简称外转换.是溶液中的激发态分子与溶剂分子或与其他溶质之间彼此碰撞而失去能量，并以热能的方式释放能量的过程.8体系间跨越（intersystem crossing）：处于激发态分子的电子发生自旋反转而使分子的多重性发生变更的过程.9磷光：经过体系间跨越的分子再通过振动弛豫降至激发三重态的最低振动能级，然后返回到基态的各个振动能级而发出光辐射，称磷光.10荧光寿命（fluorescence life time）：指除去激发光源后，分子的荧光强度降低到最大荧光强度的1/e所需的时间.11荧光效力（fluorescence efficiency）：又称荧光量子产率(fluorescence quantum yield).是激发态分子发射荧光的光子数与基态分子接收激发光的光子数之比.12荧光熄灭（fluorescence quench）：又称荧光猝灭，是指荧光物资分子与溶剂分子或其他溶剂分子彼此感化惹起荧光强度降低的景象.13荧光熄灭法（fluorescence quenching method）:如果一个荧光物资加入某种熄灭剂后，荧光强度的减弱和荧光熄灭剂的呈线性关系，利用这一性质测定荧光熄灭剂的含量.14瑞利光（Rayleigh scattering light）：光子和物资分子发生弹性碰撞时，不发生能量的交换，仅仅是光子活动方向发生改变，这类散射光叫做锐利光，波长与入射波长不异. 15拉曼光（Raman scattering light）：光子和物资分子发生非弹性碰撞时，不发生能量的交换，在光子活动方向发生改变的同时，光子与物资分子发生能量的交换，而发射出比入射光稍长或稍短的光，这类散射光称为拉曼光.16 Stokes位移与激发或接收波长比拟荧光发射波长更长称为Stokes位移.第十二章1红外接收光谱法(infrared absorption spectroscopy; IR):根据样品的红外接收光谱进行定性定量及测定分子结构的方法.2振动自在度：是分子基本振动的数目，即分子的独立振动数.3简并：以CO2为例，两个双键的振动方式分歧，但振动频率不异，接收红外线的频率不异，只能观察到一个接收峰，这类景象称简并.是基本振动接收峰数少于振动自在度的首要缘由.4红外活性振动：惹起偶极矩变更的振动. 5红外非活性振动：不克不及惹起惹起偶极矩变更的振动.6基频峰：分子接收必定频率的红外线，若振动能及由基态（V=O）跃迁至第一振动激发态（V=1）时，所发生的接收峰.7倍频峰：分子接收必定频率的红外线，又基态跃迁到第二激发态第三激发态发生的接收峰分别称为二倍频峰三倍频峰，总称为倍频峰.8泛频峰：倍频峰，合频峰及差频峰统称为泛频峰.9电子效应（electron effect）:由化学键的电子分布不均惹起.包含引诱效应和共轭效应.10引诱效应（inductive effect）:吸电子基团的引诱效应的存在，常使接收峰向高频方向挪动.11共轭效应：是接收峰向低频方向挪动.12费米共振（fermi resonance）：由频率附近的泛频峰与基频峰的彼此感化而发生的，结果使泛频峰的强度添加或发生分裂.13特征区：4000-1300cm-1,每一个接收峰都喝必定的基团绝对应，该区接收峰稀少易识别.14指纹区：1300-400 cm-1，接收峰密集复杂，如人的指纹普通，体现化合物的光谱特征性很强.15特征接收峰（characteristic absorption band）：是能用于鉴别基团存在的接收峰16相干接收峰（correlation absorption band）:是由一个基团发生的一组彼此具有依存关系的接收峰，简称相干峰.第十三章1原子接收分光光度法（atomic absorption spectrophotometry,AAS)：是基于蒸汽中的基态原子对特征电磁辐射的接收来测定试样中该元素含量的一种仪器分析方法.2共振线：原子在基态与第一激发态之间跃迁发生的谱线称为共振线，通常是最强的谱线.3天然宽度（natural width）:在无外界条件的影响下，谱线的固有的宽度.4多普勒变宽（Doppler broadening）:由无规则的热活动发生的变更，所以又称为热变宽.5压力变宽（pressure broadening）：是因为吸光原子与蒸汽华夏子彼此碰撞而惹起能级的巨大变更，使发射或接收的光量子频率改变而导致的变宽.6赫鲁兹马克变宽(Holtsmark broadening):是指被测元素激发态原子与基态原子彼此碰撞惹起的变宽，随原子蒸汽浓度添加而添加，又称共振变宽.7劳伦茨变宽(lorentz broadening)：指被测元素原子与其他外来粒子（原子，分子，离子，电子）彼此碰撞惹起的变宽，称为洛伦茨变宽.洛伦茨变宽随原子区内原子蒸气压力增大和温度升高而增大.8灵敏度：必定浓度时，测量值的增量与呼应的待测元素。

注射用氨苄西林钠质量研究周晓溪,李青翠,郭景文,崔广青,邓自新,付晓丽(山西省药品检验所,太原030001)摘要 目的:对不同生产工艺氨苄西林钠的质量进行对比研究。

方法:采用粉末X -射线衍射、电镜扫描、红外光谱、有关物质等检测方法,同时进行加速试验,综合评价不同工艺产品。

对产品中有机溶剂残留量和溶媒结晶工艺产品的2-乙基己酸残留进行检测。

结果:溶媒结晶工艺样品为结晶型粉末,冷冻干燥和喷雾干燥工艺样品为无定型粉末。

溶媒结晶工艺样品的有关物质明显较低,且产品稳定性好。

结论:研究表明溶媒结晶工艺生产的原料最为稳定,应当引导企业主动使用该原料。

关键词:注射用氨苄西林钠;质量;研究中图分类号:R 917文献标识码:A文章编号:0254-1793(2011)05-0875-04St udy on t he quality of a mpicilli n sodi u m for i njectionZ HOU X i ao-x ,i LI Q i ng-cu,i GUO Ji n g-w en ,CU I Guang-qi ng ,DENG Zi-x i n ,F U X iao-li(Shanx i Institute for D rug Contro ,l T a i yuan 030001,Chi na)Abstract Obj ective :To st u dy the qua lity o f differe n t process for pr oduction of a m picilli n sodiu m.M et hods :By usingpo wder X-ray diffracti o n ,scanning electron m icroscope ,infrared spectr oscopy ,re lated substances deter m i n ation ,ac ce lerated sa m ples were analyzed .The resi d ual so l v ents of a m picilli n sodi u m and 2-ethy lhexano ic acid of crysta lline sa m ples were deter m i n ed .Results :Solvent crysta llinzation process sa m ples are crysta lline po wder ,freeze drying and spray dry i n g process products w ere a morphous po wder .Re lated substances of so l v ent crysta llinzation process sa mp les w ere much lo w er and the pr oduction w asmore stable .Concl u sion :Stud i e s have sho wn that the ra w m ateria ls o f so lvent cr ystalli n zati o n process of production is the m ost sta b le and shou l d be used by gu i d ing the enter prises .K ey w ords :a m p icillin sod i u m f o r injection ;quality ;study第一作者 Te:l (0351)2021344;E -m ai:l z houx i aoxi 1134@126.co m氨苄西林钠问世于20世纪70年代,为广谱半合成青霉素类抗生素,作用与青霉素基本相同,适用于敏感菌所致的呼吸道感染、胃肠道感染、尿路感染、软组织感染、心内膜炎、脑膜炎、败血症等,通过抑制细菌细胞壁合成发挥抗菌作用。

2 Pfg 1169/08.2007 Requirements for cables for use in photovoltaic-systemsContentsSeite Foreword (3)1Scope (3)2Normative references (3)3Terms and definitions (5)4Halogen-free PV-cable (6)4.1Code designation (6)4.2Characteristics (6)4.3Construction (6)4.4Test (8)4.5Guideline for use (informative) (8)4.6Current carrying capacity (8)Annex A (normative) Test of mutual influence (15)Annex B (normative) Test of absence of halogen (16)Annex C (normative) Determination of halogens – Elemental test (17)Annex D (normative) Test of long term resistance of insulation to D.C (19)Annex E (normative) Cold impact test (20)Annex F (normative) Dynamic penetration test (21)Annex G (normative) Notch propagation (23)Figure 1 – Arrangement of marking (8)Figure F.1 – Arrangement for penetration test (22)Table 1 – Current carrying capacity of PV-cables (9)Table 2 – Conversion factor for deviating temperatures (9)Table 3 – Tests for halogen free PV-cable (10)Table 4 – Requirements for halogen free insulation and sheath compounds (13)Table A.1 – Requirements (15)Table B.1 – Test method, measurement, requirements (16)Table B.2 – Test sequence (16)Table E.1 – Parameter for cold impact test (20)ForewordThis test specification contents the requirements listed in a manuscript of the working group AK 411.2.3 …Leitungen für PV-Systeme“ of the German committee for standardization (DKE). This manuscript is intended to be published as German pre-standard. Up to the date of publishing of the pre-standard this test-specification of TUV Rheinland will be used for test and assessment of cables for use in PV-systems (PV-cables).1 Scope2 PfG 1169/08.2007 applies to flexible single-core cables (cords) for use at the DC-side of photovoltaic-systems with a maximum permissible voltage of DC 1,8 kV (conductor/conductor, non earthed system).The cables are suitable for use in safety class II.It is permitted to connect these cables as multiple-construction.The cables are intended to operate at ambient temperature until 90°C2 Normative referencesThe following referenced documents are indispensable for the application of this document. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies.IEC 60364-5-52, Erection of low voltage installations –Part 5: Selection and erection of electrical equipment –Chapter 52: Wiring systemsEN 50267-2-1, Common test methods for cables under fire conditions – Tests on gases evolved during combustion of materials from cables – Part 2-1: Procedures – Determination of the amount of halogen acid gas;EN 50267-2-2, Common test methods for cables under fire conditions – Tests on gases evolved during combustion of materials from cables – Part 2-2: Procedures – Determination of degree of acidity of gases for materials by measuring pH and conductivity;EN 50305, Railway applications – Railway rolling stock cables having special fire performance – Test methodsEN 50395, Electrical test methods for low voltage energy cables;EN 50396, Electrical test methods for low voltage energy cables;EN 60068-2-78, Environmental testing - Part 2-78: Tests -Test Cab: Damp heat, steady state (IEC 60068-2-78)EN 60216-1, Electrical insulating materials - Properties of thermal endurance - Part 1: Ageing procedures and evaluation of test results (IEC 60216-1);EN 60216-2, Electrical insulating materials – Thermal endurance properties – Part 2: Determination of thermal endurance properties of electrical insulating materials – Choice of test criteria (IEC 60216-2);EN 60228, Conductor of insulated cables (IEC 60228)EN 60332-1-2, Tests on electric and optical fibre cables under fire conditions – Part 1-2: Test for vertical flame propagation for a single insulated wire or cable – Procedure for 1 kW pre-mixed flame; (IEC 60332-1-2)EN 60684-2, Flexible insulating sleeving – Part 2: Methods of test (IEC 60684-2)EN 60811-1-1, Insulating and sheathing materials of electric cables – Common test methods Part 1-1: General application – Measurement of thickness and overall dimensions – Test for determining the mechanical properties (IEC 60811-1-1)EN 60811-1-2, Insulating and sheathing materials of electric and optical cables – Common test methods. Part 1-2: General application. Thermal ageing methods (IEC 60811-1-2)EN 60811-1-3, Insulating and sheathing material of electric and optical cables – Common test methods – Part 1-3: General application – Methods for determining the density – Water absorption tests – Shrinkage test (IEC 60811-1-3)EN 60811-1-4, Insulating and sheathing materials of electric and optical cables – Common test methods. Part 1-4: General application. Tests at low temperature. (IEC 60811-1-4)EN 60811-2-1, Insulating and sheathing materials of electric and optical cables – Common test methods – Part 2-1: Methods specific to elastomeric compounds – Ozone resistance, hot set and mineral oil immersion tests (IEC 60811-2-1)EN 60811-3-1, Insulating and sheathing materials of electric cables – Common test methods Part 3-1: Methods specific to PVC compounds – Pressure test at high temperature, test for resistance to cracking (IEC 60811-3-1)HD 22.13, Rubber insulated cables of rated voltages up to and including 450/750 V Part 13: Single and multicore flexible cables, insulated and sheathed with crosslinked polymer and having low emission of smoke and corrosive gases;HD 605, Power cables – Part 605: Additional test methodsHD 60364-7-712Electrical installations of buildings – Part 7-712: Requirements for special installations or locations – Solar photovoltaic (PV) power supply systems (IEC 60364-7-712, modified)3 Terms and definitionsFor the purposes of this document, following definitions apply.3.1 Terms for test procedure3.1.1Type test (symbol T)Tests required to be made before supplying a type of cable covered by this standard on a general commercial basis, in order to demonstrate satisfactory performance characteristics to meet the intended application. These tests are of such a nature that, after they have been made, they need not be repeated, unless changes are made in the cable materials or design or manufacturing process which might change the performance characteristics.3.1.2sample tests (symbol S)Tests made on samples of completed cable or components taken from a completed cable, at a specified frequency, so as to verify that the finished product meets the specified requirements.3.1.3Routine tests (symbol R)Tests made by the manufacturer on each manufactured length of cable to check that each length meets the specified requirements3.2Rated voltageThe rated voltage of the cable determines the construction and the tests of the cable with regard to the electrical properties.The rated voltage is designated by two values of frequency voltage: U0/U in VoltU0 rated power frequency voltage between conductor and earth (metallic screen of cable or ambient medium);U rated power frequency voltage between two conductors of a multipole cable or of a system of single core cables.The rated voltage of the cable for a given application shall be suitable for the operating conditions in the system in which the cable is used.This requirement is applicable for both U o and UThe rated voltage between two conductors in a DC-system shall not exceed the 1,5 time value of rated voltage U of the cable, and the rated voltage between conductor and earth shall not exceed the 1,5 time value of rated voltage U o of the cable.NOTE The operating voltage of a system may exceed is rated voltage permanent for 20%. A cable may be operated with a voltage which value is 20% higher than rated voltage under condition that the rated voltage is not less than the rated voltage of the system.3.3DC sidepart of a PV installation from a PV cell to the DC terminals of the PV inverter3.4open-circuit voltage under standard test conditions U OC STCvoltage under standard test conditions across an unloaded (open) PV module, PV string, PV array, PV generator or on the DC side of the PV inverter3.5short-circuit current under standard test conditions I SC TCshort-circuit current of a PV module, PV string, PV array or PV generator under standard test conditions4 Halogen free PV-cable4.1 Code designationPV1-F4.2 Characteristics4.2.1 Rated voltageAC U0/U 0,6/1 kVDC 1,8 kV (conductor-conductor, non earthed system, circuit not under load).If the cable is used in DC-systems the rated voltage between two conductors shall not exceed the 1,5 time value of rated voltage U of the cable. In with single-phase earthed DC-systems this value shall be multiplied with factor 0,5.4.2.2 Temperature rangeAmbient temperature: –40 °C to +90 °CMax. temperature at conductor: 120 °CThe cables are intended to operate at ambient temperature until 90°C. For this a temperature index of 120°C applies to the insulation and the sheath, based on EN 60216-1 (20.000h, 50% residual elongation).Note The expected period of use is 25 years.The permitted short-circuit-temperature refer to a period of 5s is 200°C.4.3 Construction4.3.1 ConductorNumber of conductors: 1The conductor shall be class 5, according to EN 60228.The single wires must be tinned.Preferred diameters: 2,5, 4, 6, 10, 16 mm24.3.2 Separation layerA separation layer of a suitable halogen free material may be applied around the conductor.4.3.3 InsulationThe insulation shall be a suitable halogen free material applied around the conductor.The insulation shall be extruded and shall consist of one or several adjacent adherent layers. It shall be solid and homogeneous, it must be possible to remove it without damage to the insulation itself, to the conductor and to the tin coating.The insulation shall be smooth, consistently applied and largely circular. Compliance shall be checked by inspection and by manual test.The wall thickness of insulation is specified by the manufacturer, but it must not fall short of the minimum value of 0,5mm.4.3.4 Separation layerA separation layer of a suitable halogen free material may be applied around the insulation.4.3.5 SheathThe core must be covered by a sheath.The sheath around the core must be of a suitable halogen free material.The sheath shall be extruded and shall consist of one or several adjacent adherent layers. The sheath shall be smooth and consistently applied.The wall thickness of sheath is specified by the manufacturer, but it must not fall short of the minimum value of 0,5mm.4.3.6 Outer diameterThe average value of the outer diameter shall be within the limits specified by the manufacturer.4.3.7 Multiple constructionEach single-core cable in a multiple construction shall pass the requirements of this document. Each additional component in a multiple construction shall pass the requirements of this document.4.3.8 Marking4.3.8.1 GeneralThe cable shall be marked as follows:a) Trademark;b) Code designation;c) Rated diameter.Marking may be by printing or by reproduction in relief on or in the sheath.4.3.8.2 TrademarkCables shall be provided with an indication of the manufacturer, which consist of a consecutively marking with company name or company sign or with (if trademarked) an identification number.4.3.8.3 Code designationCables shall be provided with an code designation according to 4.1 applied consecutively on sheath.4.3.8.4 Arrangement of markingEach marking is considered as consecutive if the spacing between the end of a marking and the begin of the following identical marking does not exceed following value:– 550mm, for marking on sheath or outer jacket.Following figure shows an example of marking on sheath.Figure 1 – Arrangement of marking4.3.8.5 DurabilityPrinted markings shall be durable. Compliance with this requirement shall be checked by the test given in 5.1 of EN 50396.4.3.8.6 LegibilityEach marking shall be legible.4.4 TestCompliance with the requirements of 4.3 shall be checked by visual inspection and tests according to table 3.4.5 Guideline for use (informative)Cables according to this standard are intended for use in PV-systems according to EN 60364-7-712.4.6 Current carrying capacityAmbient temperature: 60°CMax. temperature at conductor: 120 °CTable 1 – Current carrying capacity of PV-cablesKind of installationRated diameter Single cable free inair Single cable onsurfacesTo cables adjacent onsurfacesmm2 A A A 1,5 30 29 24 2,5 41 39 33 4 55 52 44 6 70 67 57 10 98 93 79 16 132 125 107 25 176 167 142 35 218 207 176Table 2 – Conversion factor for deviating temperaturesAmbient temperature Conversion factor°CUp to 60 1,0070 0,9180 0,8290 0,71100 0,58110 0,41Table 3 – Tests for halogen free PV-cable1 23 45Test method described in Ref. No. TestRequirementsCategoryof teststandardclause1 Electrical tests1.1 Resistance of conductorsT,S EN 50395 5 1.2 Voltage test on completed cable with AC or DC T,S EN 503956– AC-test-voltage kV– DC- test-voltage kV Length of sample m Duration of testmin Temperature of the water°C 6,5 15 20 5 20 ± 5 1.3 Absence of faults at complete cable – AC-test-voltage kV 10 R EN 50395 10 1.4Surface resistance of sheath – Minimum value Ω 109 TEN 50395111.5Insulation at complete cable Length of sample m Duration of testh Temperature of the water °C – Minimum value at 20 °C Ω ⋅ cm – Minimum value at 90 °CΩ ⋅ cm5 2 20± 5 1014 1011 T EN 50395 81.6 Long term resistance of insulation to d.c. T Annex D2 Constructional and dimensional tests2.1 Checking of compliance with constructional provisionsT,S Inspection and manual tests2.2 Measurement of thickness of insulation T,S EN 50396 4.1 2.3 Measurement of thickness of sheath T,S EN 503964.2 2.4 Measurement of overall dimensions 2.4.1 – Mean valueT,S EN 50396 4.4 2.4.2 –Ovality%≤ 15 T,S EN 50396 4.4 3 Pressure test at high temperature at complete cable T EN60811-3-13.1 Test conditions:– temperature°C 140 ± 3 – duration of heating under load min240 – Coefficient k 0,6 3.2 Results to be obtained:– depth of penetration, max.%50 – Voltage test 10 min after exculpation andcoolingTable 4, 1.24 Damp heat test T EN 60068-2-784.1 Test conditions:– temperature °C 90 – duration h 1000 – relative humidity %85 4.2 Results to be obtained:– variation of tensile strength max. % – 30– variation of elongation at breakmax. %– 30No. of test standard clause 5 Resistance against acid and alkalineT EN 60811-2-1 10 solution5.1Chemical stressacid: N-Oxal-acidalkaline solution: N-sodium hydroxide solutiontemperature °C 23duration h 1685.2Tensile strength:variation, max. % ± 305.3Elongation at break, min. % 1006 Test of influence T Annex A7 Cold impact test at –40 °C T Annex E8 Cold bending testT EN 60811-1-4 8.2 Diameter of cable < 12,5 mm8.1 Test conditions:– temperature °C –40 ± 2– duration of conditioning h 16 EN 60811-1-4 8.2.3 8.2 Results to be obtained Absence ofcracks9 Cold elongation testTable 3 Diameter of cable ≥ 12,5 mm10 Ozone resistance at complete cable T10.1 Method B EN 50396 8.1.3– temperature °C 40 ± 2– relative humidity % 55 ± 5– duration h 72(200 ± 50) × 10–6– Ozone concentration %(by volume)10.2 Results to be obtained Absence ofcracks.11 Weathering/UV-resistance T HD 605/A1 2.4.20 11.1 Conditions:– duration h 720– temperature °C63(Black-Standard-temperature)– relative humidity % 6560 ± 2– min. power at W/m2wavelength 300 nm to 400 nm– duration spraying/drying min 18/102Results to be obtained Absence ofcracks.12 Dynamic penetration test T Annex F13 Notch propagation T Annex GNo. of test standard clause 14 Shrinkage test at complete cable T EN 60811-1-3 11((sheath)) 14.1 Conditions:– temperature °C 120– duration h 1– Distance L of sample mm 30014.2 Results to be obtained:– Maximum shrinkage. % 215 Test under fire conditionsT, S EN 60332-1-215.1 Test for vertical flame propagation at completecable15.2 Assessment of halogen T, S15.2.1 Absence of halogen Annex B 15.2.2 Determination of halogens – Annex CTable 4 – Requirements for halogen free insulation and sheath compounds1 2 3 4567Test method described in Type of compound Ref. No. TestUnitstandardclauseinsulationsheath1 Mechanical characteristics1.1Properties before ageingEN 60811-1-19.2 1.1.1 Values to be obtained for the tensile strength:– median, min.N/mm 2 6,5 8,0 1.1.2 Values to be obtained for the elongation atbreak: – median, min.%125 125 1.2Properties after ageing in ovenEN 60811-1-28.1 1.2.1 Ageing conditions: – temperature °C 150 ± 2 150 ± 2– duration of treatmenth 7 × 24 7 × 24 1.2.2 Values to be obtained for the tensile strength:c – median, min. N/mm 2 – –– variation, max.% –30a –30a 1.2.3 Values to be obtained for the elongation atbreak:c – median, min. % – – – variation, max. %– 30a – 30a 1.3 Hot set test dEN 60811-2-19 1.3.1 Conditions– Temperature °C 200± 3 200± 3 – Time under load min 15 15– mechanical stressN/cm 2 20 20 1.3.2 Values to be obtained – elongation under load, max.% 100 100 – permanent elongation after cooling, max. % 25 25 1.4Thermal endurance propertiesEN 60216-21.4.1 ConditionsEither test of elongation at break or bending test shall be performed.– Temperature index 120 120 – elongation at break c % 50 50 – bending test EN 50305 7.2 2 D 2 D 1.5Cold elongation testEN 60811-1-48.4 1.5.1 Conditions: – temperature °C–40 ± 2–40 ± 2– durationh EN 60811-1-4 8.4.4 und 8.4.5bb1.5.2 Values to be obtained:– elongation at break, min.%30301 2 3 4 5 6 7Test method described in Type of compound Ref. No.TestUnitstandardclauseinsulationsheatha No positive value for variation fixed.b See test method in column 4 and 5.c This test shall be performed at test samples of insulation and sheath compound. d This test shall be performed only at cross-linked insulation and sheath compoundTest of mutual influenceA.1 ConditionsTest samples must be aged for 7 days at (135 ± 2) °C at conditions according to table 2A.2 RequirementsAfter ageing the insulation and the sheath shall pass the requirements of table A.1.Table A.1 – RequirementsTests units insulation sheath Tensile strength – median, min. N/mm2– –– variation a, max. % ± 30 –30 b Elongation at break – median, min. % – –– variation a, max. % ± 30 ± 30a Variation: difference between the median value obtained after ageing and the median value obtained without ageing expressed as apercentage of the latter.b Positive tolerances are not limited.Test of absence of halogenB.1 Requirements of extruded materialsInsulation and sheath shall pass the requirements as follows: a) Type testThe material must be tested as described in table B.1.Table B.1 – Test method, measurement, requirementsTest methodMeasurementrequirements1 EN 50267-2-2 pH and conductivity pH ≥ 4,3 undconductivity ≤ 10 µS/mm a 2 EN 50267-2-1 Chlorine- and Bromine content, expressed in HCI ≤ 0,5 %3aAnnex CHalogen: FluorideIf negative the test should be finished. No further test is necessary.The material shall be accepted.If positive, test of 3b shall be performed 3bEN 60684-2Fluoride content≤ 0,1 %a If discrepancies regarding conductivity appear, e.g. the recommended value is exceeded even if there is compliance with therecommended ph-value, other test method may be applied after agreement with all participants.The material shall be tested according to test sequence of table B.2.Table B.2 – Test sequenceTest method MeasurementValue ResultIf negative the test should be finished. No further test is necessary.The material shall be accepted. Phase 0 HD 22.13,Annex CHalogen: Fluoride, Chloride and BromideIf positive continue with phase 1.< 4,3 The material shall be revised. pH ≥ 4,3Conductivity shall be tested. conductivity ≤ 2,5 µS/mmThe material shall be accepted. No further test is necessary.conductivity > 10 µS/mm The material shall be revised.Phase 1 EN 50267-2-2 conductivity (s)> 2,5 µS/mm but ≤ 10 µS/mm Test according to EN 50267-2-1 shall be performed > 0,5 % The material shall be revised.Phase 2 EN 50267-2-1Chlorine- and Bromine content, expressed in HCI≤ 0,5 % Test according to EN 60684-2 shall be performed. > 0,1 % The material shall be revised. Phase 3 EN 60684-2Fluoride content≤ 0,1 %The material shall be accepted.Determination of halogens – Elemental testWarningOwing to its potentially hazardous nature, the fusion operation should be carried out in a fume cupboard, using a safety screen.C.1 EquipmentBunsen burner3 small/medium soda glass test tubes (approximately 50 mm x 10 mm)Test tube holderEvaporating basin/mortarWire gauze;FunnelFilter paperC.2 MaterialsUnknown sampleSodium metalDilute nitric acid (5 %)Aqueous silver nitrate (5 %)Dilute ammonia (10 %)Freshly made up zirconium-alizarin red S reagentGlacial acetic acidAcid/pH indicator papersC.3 ProcedureC.3.1 Sodium fusionPlace 200 mg – 250 mg of the sample into the bottom of a small soda glass test tube. Add 10 ml of distilled/de-ionized water to the evaporating basin and place this in the fume cupboard behind the safety screen. Whilst holding the test tube firmly with the test tube holder at an angle of 45° - 60° to the vertical, introduce a piece of freshly cut, clean sodium (about the size of a small pea) (200 mg – 250 mg) into the mouth of the test tube without allowing it to come into contact with the sample. With the safety screen in place, heat the sodium gently until it melts and runs down on to the sample (there may be a vigorous reaction when the molten sodium reaches the sample if halogens are present). Heat the tube gently for about 1 min, then more strongly until the lower 20 mm of the tube glows red hot. Plunge the red hot tube into the water in the evaporating basin, immediately placing the gauze on top. (The gauze prevents any loss of material when the tube shatters on contact with the water.) Allow any non reacted sodium to react before grinding up the solution and glass. Filter, and separate the filtrate into two equal portions.C.3.2 Chlorine and bromineTo the first portion of the filtrate, add sufficient nitric acid to make the solution acidic. Boil this solution until its total volume has been reduced by half (this is to remove any HCN or H2S, if present, which would interfere with the test). Add 1 ml silver nitrate solution; a white or yellowish-white precipitate indicates the presence of halogen (Cl, Br) in the original sample. (If the liquor is decanted, and the precipitate is white and readily soluble in dilute ammonia, then chloride is present.)C.3.3 FluorineTo the second portion of the filtrate, acidify with glacial acetic acid. Boil this solution until its total volume has been reduced by half. Add 2 to 3 drops freshly prepared zirconium lake reagent (equal volumes of: a) Alizarin solution: 0,05 g Alizarin Red-S in 50 ml distilled water, b) Zirconium solution: 0,05 g zirconium nitrate in 10 ml concentrated HCl diluted with 50 ml distilled water). Heat at 40 °C for 1 h. The presence of fluoride is indicated by the red/pink colouration being bleached to yellow.Test of long term resistance of insulation to D.C.A test sample with a length of minimum 5m shall be immersed into water containing 3 % NaCl. Further on minimum 300mm of the sample shall stick out of the water. The water-bath shall be retained for (240 ± 2) h at a high temperature of (85 ± 2) °C and a D.C.-voltage 0,9kV shall be applied between conductor and water whereby the conductor shall be connected to the positive potential.The current of this circuit shall be measured with a period of not more than 24h. If possible a continuous measurement shall be preferred.The measured values shall be recorded in a time-current-curve which identifies a stable progress.NOTE A stable progress is e.g. an increase of less than 10% of leakage current on the average for a time of 24h (This is part of the inspection based on practical experiences)After storing the samples shall be taken out of the salt-water-solution and a voltage test according to Ref.-No. 1.2 of table 1 shall be performed. The test voltage shall be the rated voltage (U) of the cable.Cold impact testThe cold impact test shall be performed at –40°C according to clause 8.5 of EN 60811-1-4, but the mass of hammer, the mass of test probe and the height shall comply with table 2.Table E.1 – Parameter for cold impact testDiameter of cable (D) Mass of hammer Mass of test probe height mm g g mmD < 15 1 000 200 10015 < D≤ 25 1 500 200 150D > 25 2 000 200 200The inner and outer surface of sheath shall be inspected with normal or corrective visual faculty without magnification. Only the outer surface of the insulation shall be inspected. No cracks must be determinedAnnex F(normative)Dynamic penetration testA test apparatus for pull test (or a equivalent apparatus) shall be operated in pressure modus and shall be equipped with a measuring device which is able to record the force of penetration of the spring-steel-needle (see figure F.1b) through the insulation or sheath of a completed cable. A circuit with low voltage which finish the test at the moment when the needle penetrates the insulation or the sheath and makes contact with the conductor shall be added.The test shall be performed at room temperature. The force applying to the needle shall be increased continuously with 1 N/s until contact with the conductor has been made. 4 tests at each sample shall be performed and the force at the moment of contact shall be recorded. After each test the sample shall be moved forward and shall be turned clockwise for 90°.The mean value of the 4 test results must not be less than the minimum value F determined with following formulaF = 50 ⋅DD diameter of cable in mmDimensions in mma) detail X(edges not broken or rounded, without ridge)b) detail YCaption 1 N.A. 2 N.A. 3 Load 4 Clamp 5 Sample6Mounting surface7 Fixing screw 8 Blade9 Shoulder with sufficient depth for testing the insulation 10 Needle of spring steel 11SampleFigure F.1 – Arrangement for penetration testAnnex G(normative)Notch propagationThree samples of the cable shall be notched, to a depth of 0,05 mm of the insulation or sheathing, at four points equally spaced with respect to one another around the circumference and 25 mm apart along the length, and in a plane mutually perpendicular to the conductor.One of the samples shall be conditioned at -15 °C, one at ambient temperature and one at 85 °C, in all cases for 3 h, after which time they shall be wound on to a mandrel, (3 ± 0,3) times the minimum specified diameter of the cable, whilst at the conditioning temperature. The notched sample shall be wrapped around the mandrel such that at least one notch is on the outside of the cable.The sample shall be allowed to return to ambient temperature and then subjected to the voltage test given in no. 1.2 of Table 1 but at half the rated voltage U0.。

2021年2月名油狄旅4淨參找第56卷第1期•处理技术•文章编号：1000-7210(2021)01-0057-05应用S V D约束的迭代反演混叠噪声压制方法董烈乾*张慕刚骆飞张翊孟王泽魏国伟(东方地球物理公司，河北涿州072751)董烈乾，张慕刚，骆飞，张翊孟，王泽，魏国伟.应用S V D约束的迭代反演混叠噪声压制方法.石油地球物理勘2021,56( 1) ：57-61,117.摘要超高效混叠采集技术可实现多组震源同时激发产生地震波场，大幅度提高采集效率，但往往会导致相邻震源之间产生波场交叉而相互干涉，显著降低地震数据的信噪比。

为此，提出一种基于奇异值分解（S V D)约束迭代反演的混叠噪声压制方法。

首先以选定区域的混叠噪声奇异值对混叠数据的奇异值向量进行约束，然后利用迭代反演的策略逐步更新混叠数据的奇异值向量.最终在共炮检距域或动校正后的共中心点域实现混叠噪声与有效信号的分离。

数据测试结果表明，该方法可在压制混叠噪声的同时，充分地保护有效信号。

关键词超高效混叠采集奇异值分解（S V D)混叠噪声迭代反演中图分类号：P631文献标识码：A doi： 10. 13810/j. cnki. issn. 1000-7210. 2021. 01. 006〇引言近年来，随着高效地震采集技术的发展以及在地震勘探领域的广泛应用，陆上宽方位和高密度地震采集成为可能。

高效地震采集技术的应用不仅大 幅度提高了生产效率，能获得高覆盖次数的地震资料，而且极大地改善了地震资料品质。

超高效混叠 采集技术[1]采用多组可控震源独立激发，各组间无 等待时间，对可控震源数量无特别限制；且可控震 源数量越多，采集施工效率越高。

但采用多组震源不同激发点位同时激发，必然在原始单炮记录上产生很强的邻炮干扰，即混叠噪声，显著降低地震数据 的信噪比，影响后续地震数据处理质量。

根据超高效混叠采集的特点，相同接收排列记 录了不同震源在不同点位的不同时间激发的能量。