美国药典滴定液配制及标定方法——中文翻译

<791>pH对于药典用途，pH定义为由合适的，正确标定的，使用对氢离子活度敏感的指示电极，玻璃电极，及适当的参比电极，具有重复pH值至0.02单位的电位计或酸度计(pH 计)给定的值。

仪器应能够指示通过电极对的电势，对于pH标定，通过操纵“标定”，“调零”，“不对称”或“校正”控制调节电路的电势，并应可以通过“温度”和“斜率”控制来控制每单位毫伏的变化改变pH读数。

除了在单个专论中有特殊说明的外，测量在25 ± 2℃下进行。

pH值由以下方程式定义：pH = pHs + (E – E S)/k其中E 和 E S分别是检测中原电池所包含溶液测定的电势，由pH表示，及合适的标定缓冲溶液，用pHs表示。

K值是每单位pH 值的改变所对应改变的电势，理论上在任何温度t下它都应为[0.05916 + 0.000198(t – 25℃)]伏。

需要强调的是pH定义，pH尺度和标准缓冲液的指定值都是为了确定一个实际的，可操作的操作系统，以便在实验室间进行结果对比。

因此测定的pH值与根据定义pH =–log a H+计算出的pH值并不精确符合。

只要被测溶液与标准缓冲液中的成分充分接近，测定的pH值就与理论pH值十分接近了。

尽管没有关于测量氢离子活度或浓度的系统适应性要求的制定，在水溶液中得到的值仍与相应的氢离子活度相近。

如果通过用标准缓冲液校正pH计，然后用该pH计来测量非水溶液或悬浮溶液的“pH”值，酸碱的电离常量，溶剂的介电常数，液接界电势（可能有近似1单位pH 的误差）和玻璃电极氢离子响应值都发生改变。

基于这些原因，性状为部分水溶液的溶液得到的pH值只是一个表观pH值。

pH计标定用的缓冲溶液标准缓冲溶液的制备描述如附表*所述。

必需纯度的缓冲盐可通过国家科学院（National Institute of Science and Technology）得到。

溶液应贮藏在带有密封装置的或有二氧化碳吸收管（苏打石灰）的硬质玻璃瓶或聚乙烯瓶中。

文件名称滴定液（标准液）配制、标定、使用管理规程一、目的：建立滴定液（标准液）管理制度，以规范其配制、标定、使用分发和贮存管理。

二、适用范围：适用于质检中心所有滴定液、标准液。

三、责任者：质检中心全体人员。

四、内容：1、术语1.1 滴定液：指在容量分析中用于滴定被测物质含量的标准溶液，具有准确的浓度（取4位有效数字）。

滴定液的浓度以“mol/L”表示，其基本单位应根据药典或GB标准规定。

1.2F值：滴定液的浓度值与其名义值之比，称为“F”值，常用于容量分析中的计算。

1.3标定：系指根据规定的方法，用基准物质或已标定的滴定液准确测定滴定液浓度（mol/L）的操作过程。

2、滴定液配制仪器与用具：2.1 分析天平其分度值应为0.1mg；毫克组砝码需经校正，并列有校正表备用。

2.2 10、25和50ml滴定管应附有该滴定管的校正值。

2.3 10、15、20和25ml移液管其真实容量应经校准，并附有校正值。

2.4 250ml、500ml、1000ml量瓶应符合国家A级标准，或附有校正值。

3、滴定液配制所需试药与试液3.1 使用中国药典现行版规定试药和试液。

3.2 基准试剂应有专人负责保管与领用。

4、配制滴定液的配制方法有间接配制法与直接配制法两种，应根据规定选用，并应遵循下列有关规定。

4.1 配制滴定液所使用的试剂为分析纯或基准试剂，配制前检查封口及包装情况，应无污染。

4.2 在规定的使用期内，所用溶剂“水”，在未注明有其他要求时，应符合中国药典“纯化水”项下的规定。

4.3 采用间接配制法，溶质与溶剂的取用量均应根据规定量进行称取或量取，并使制成后滴定液的浓度值应为其名义值的0.95~1.05（即±5%范围）；如在标定中发现其浓度值超出其名义值的0.95~1.05范围时，应加入适量的溶质或溶剂予以调整。

当配制量大于1000ml时，其溶质与溶剂的取用量均应按比例增加。

4.4 采用直接配制法时，其溶质应采用“基准试剂”，并按规定条件干燥至恒重后称取，取用量应精密称定，并置1000ml量瓶中，加溶剂溶解并稀释至刻度，摇匀。

滴定液的配制与标定一、本规程所用水，除另有规定外，均指纯化水或重蒸馏水。

二、“精密称定”系指称取重量应准确至所取重量的千分之一；“精密量取”系指量取体积的准确度应符合国家标准中对该体积移液管的精密度要求；“量取”系指可用量筒或按照量取体积的有效数位选用量具；取用量为“约”若干时，系指取用量不超过规定量的±10％；称取，除另有规定外，指准确到0.1g三、恒重，除另有规定外，系指供试品连续两次干燥或灼烧后称重的差异在0.3mg以下；干燥至恒重的第二次及以后各次称重均应在规定条件下继续干燥1小时后进行；炽灼至恒重的第二次称重应在继续炽灼30分钟后进行。

四、本规程使用的滴定液和试液的浓度，以mol/L表示的，其浓度要求精密标定的滴定液用“XXX滴定液（YYYmol/L）”表示；作其他用途不需精密标定时用“YYYmol/L XXX溶液”表示，以示区别。

五、溶液后标示的“（1→10）”等符合，系指固体溶质1.0g或液体溶质1.0mL加溶剂使成10mL的溶液；未注明何种溶剂时均指系水溶液；两种或两种以上的液体或混合物，名称之间用半字线“-”隔开；其后括号内所示的“:”符号，系指各液体混合时的体积（重量）比例六、百分比用“％”标示，系指重量的比例；但溶液的百分比，除另有规定外，系指溶液100mL中含溶质若干克；乙醇溶液的百分比，系指在20℃时容量的比例。

七、液体的滴，系指在20℃时，以1.0mL水为20滴进行换算。

八、温度以摄氏度（℃）表示水浴温度除另有规定外，均指98～100℃室温系指10～30℃冷水系指2～10℃冰浴系指约0℃放冷系指放冷至室温九、贮藏项下的规定，系对药品贮藏与保管的基本要求，以下列名词术语表示：遮光系指用不透光的容器保证，例如用棕色容器或黑纸包裹的无色透明、半透明容器密闭系指将容器密闭，以防止尘土及异物进入密封系指将容器密封以防止风化、吸潮、挥发或异物进入熔封系指将容器熔封或用适宜的材料严封，以防止空气与水分的侵入并防止污染阴凉处系指不超过20℃凉暗处系指遮光并不超过20℃冷处系指2～10℃常温系指10～30℃1.0 硫代硫酸钠滴定液（0.1mol/L ）Na 2S 2O 3＝248.19 24.82g →1000ml【配制】取硫代硫酸钠26g 与无水碳酸钠0.20g ，加新沸过的冷水适量使溶解成1000ml ，摇匀，放置1个月后滤过。

Many Pharmacopeial articles either are hydrates or contain water in adsorbed form. As a result, the determination of the water content is important in demonstrating compliance with the Pharmacopeial standards. Generally one of the methods given below is called for in the individual monograph, depending upon the nature of the article. In rare cases, a choice is allowed between two methods. When the article contains water of hydration, the Method I (Titrimetric), the Method II (Azeotropic), or the Method III (Gravimetric) is employed, as directed in the individual monograph, and the requirement is given under the heading Water.很多药典物品要么是水合物，要么含有处于吸附状态的水。

因此，测定水分含量对于证实与药典标准的符合性是很重要的。

通常，在具体的各论中会根据该物品的性质，要求使用下面若干方法中的一个。

偶尔，会允许在2个方法中任选一个。

当该物品含有水合状态的水，按照具体各论中的规定，使用方法I（滴定测量法）、方法II（恒沸测量法）、或方法III（重量分析法），这个要求在标题水分项下给出。

药品及生物制品的分析方法和方法验证指导原则目录1.介绍 (1)2.背景 (2)3.分析方法开发 (3)4.分析程序内容 (3)A.原则/范围 (4)B.仪器/设备 (4)C.操作参数 (4)D.试剂/标准 (4)E.样品制备 (4)F. .................................................................................................................... 标准对照品溶液的制备 (5)G.步骤 (5)H.系统适应性 (5)I.计算 (5)J.数据报告 (5)5.参考标准和教材 (6)6 分析方法验证用于新药，仿制药，生物制品和DMF (6)A.非药典分析方法 (6)B.验证特征 (7)C.药典分析方法 (8)7.统计分析和模型 (8)A.统计 (8)B.模型 (8)8.生命周期管理分析程序 (9)A.重新验证 (9)B.分析方法的可比性研究 (10)1.另一种分析方法 (10)2.分析方法转移的研究 (11)C.报告上市后变更已批准的新药，仿制药，或生物制品 (11)9.美国FDA 方法验证 (12)10.参考文献前言本指导原则草案，定稿后，将代表美国食品和药物管理局（FDA）目前关于这个话题目前的想法。

它不会创造或赋予或任何人的任何权利，不约束FDA 或公众。

您可以使用另一种方法，如果该方法符合适用的法律和法规的要求。

如果你想讨论一个替代方法，请与FDA 工作人员负责实施本指南。

如果你不能确定适当的FDA 工作人员，请拨打本指南的标题页上所列的电话号码。

介绍：该修订指南草案将取代行业2000 年的指导分析方法和方法验证草案，并最终确定后，也将取代1987 年美国FDA 行业指南《提交的样品和分析数据的方法验证》。

该草案提供了有关申请人如何提交分析程序和方法验证数据来支持说明原料药和制剂具有强度、质量、纯度和效用的文件。

SolutionsNormal Solutions —Normal solutions are solutions that contain 1 gram equivalent weight of the active substance in each 1000 mL of solution; that is, an amount equivalent to 1.0079 g ofhydrogen or 7.9997 g of oxygen. Normal solutions and solutions bearing a specific relationship to normal solutions, and used in volumetric determinations, are designated as follows: normal, 1 N; double-normal, 2 N; half-normal, 0.5 N; tenth-normal, 0.1 N; fiftieth-normal, 0.02 N; hundredth-normal, 0.01 N; thousandth-normal, 0.001 N.Molar Solutions —Molar solutions are solutions that contain, in 1000 mL, 1 gram-molecule of the reagent. Thus, each liter of a molar solution of sulfuric acid contains 98.07 g of H 2SO 4 and each liter of a molar solution of potassium ferricyanide contains 329.25 g of K 3Fe(CN)6. Solutions containing, in 1000 mL, one-tenth of a gram-molecule of the reagent are designated “tenth-molar,” 0.1 M; and other molarities are similarly indicated.Empirical Solutions —It is frequently difficult to prepare standard solutions of a desired theoretical normality, and this is not essential. A solution of approximately the desired normality is prepared and standardized by titration against a primary standard solution. The normality factor so obtained is used in all calculations where such empirical solutions are employed. If desired, an empirically prepared solution may be adjusted downward to a given normality provided it is strong enough to permit dilution.All volumetric solutions, whether made by direct solution or by dilution of a stronger solution, must be thoroughly mixed by shaking before standardization. As the strength of a standard solution may change upon standing, the factor should be redetermined frequently.When solutions of a reagent are used in several normalities, the details of the preparation and standardization are usually given for the normality most frequently required. Stronger or weaker solutions are prepared and standardized in the same general manner as described, using proportionate amounts of the reagent. It is possible in many instances to prepare lowernormalities accurately by making an exact dilution of a stronger solution. Volumetric solutions prepared by dilution should be restandardized either as directed for the stronger solution or by comparison with another volumetric solution having a known ratio to the stronger solution. Dilute solutions that are not stable, as, for instance, potassium permanganate 0.01 N and more dilute sodium thiosulfate, are preferably prepared by exactly diluting the higher normality with thoroughly boiled and cooled water on the same day they are required for use.Blank Determinations —Where it is directed that “any necessary correction” be made by a blank determination, the determination is to be conducted with the use of the same quantities of the same reagents treated in the same manner as the solution or mixture containing the portion of the substance under assay or test, but with the substance itself omitted. Appropriate blankcorrections are to be made for all Pharmacopeial titrimetric assays (see Titrimetry 541).All Pharmacopeial assays that are volumetric in nature indicate the weight of the substance being assayed to which each mL of the primary volumetric solution is equivalent. In general, these equivalents may be derived by simple calculation from the data given under Molecular Formulas and Weights, in the Reference Tables.Preparation and Methods of Standardization of Volumetric SolutionsThe following directions give only one method for standardization, but other methods of standardization, capable of yielding at least the same degree of accuracy, may be used. Thevalues obtained in the standardization of volumetric solutions are valid for all Pharmacopeial uses of these solutions, regardless of the instrumental or chemical indicators employed in the individual monographs. Where the apparent normality or molarity of a titrant depends upon the special conditions of its use, the individual monograph sets forth the directions for standardizing the reagent in the specified context. For those salts that usually are available as certified primary standards, or that are available as highly purified salts of primary standard quality, it ispermissible to prepare solutions by accurately weighing a suitable quantity of the salt anddissolving it to produce a specific volume of solution of known concentration. Acetic, hydrochloric, and sulfuric acids may be standardized against a sodium hydroxide solution that recently has been standardized against a certified primary standard.All volumetric solutions, if practicable, are to be prepared, standardized, and used at the standard temperature of 25. If a titration is carried out with the volumetric solution at a markedly different temperature, standardize the volumetric solution used as the titrant at that different temperature, or make a suitable temperature correction.Acetic Acid, Double-Normal (2 N )C 2H 4O 2, 60.05120.10 g in 1000 mLAdd 116 mL of glacial acetic acid to sufficient water to make 1000 mL after cooling to room temperature.Ammonium Thiocyanate, Tenth-Normal (0.1 N )NH 4SCN, 76.127.612 g in 1000 mLDissolve about 8 g of ammonium thiocyanate in 1000 mL of water, and standardize the solution as follows.Accurately measure about 30 mL of 0.1 N silver nitrate VS into a glass-stoppered flask. Dilute with 50 mL of water, then add 2 mL of nitric acid and 2 mL of ferric ammonium sulfate TS, and titrate with the ammonium thiocyanate solution to the first appearance of a red-brown color.If desirable, 0.1 N ammonium thiocyanate may be replaced by 0.1 N potassium thiocyanate where the former is directed in various tests and assays.Bismuth Nitrate, 0.01 MBi(NO 3)3·5H 2O, 485.071000 mL of this solution contains 4.851 g of bismuth nitrate pentahydrateDissolve 4.86 g of bismuth nitrate pentahydrate in 60 mL of dilute nitric acid, add 0.01 N nitric acid to make 1000 mL, and standardize the solution as follows.Accurately measure 25 mL of the prepared bismuth nitrate solution, add 50 mL of water and 1 drop of xylenol orange TS, and titrate the solution with 0.01 M edetate disodium VS until the red color changes to yellow. Calculate the molarity factor.Bromine, Tenth-Normal (0.1 N)Br, 79.907.990 g in 1000 mLDissolve 3 g of potassium bromate and 15 g of potassium bromide in water to make 1000 mL, and standardize the solution as follows.Accurately measure about 25 mL of the solution into a 500-mL iodine flask, and dilute with 120 mL of water. Add 5 mL of hydrochloric acid, insert the stopper in the flask, and shake it gently. Then add 5 mL of potassium iodide TS, again insert the stopper, shake the mixture, allow it to stand for 5 minutes, and titrate the liberated iodine with 0.1 N sodium thiosulfate VS, adding 3 mL of starch TS as the endpoint is approached.Preserve in dark amber-colored, glass-stoppered bottles.Ceric Ammonium Nitrate, Twentieth-Normal (0.05 N)Ce(NO 3)4·2NH 4NO 3, 548.222.741 g in 100 mLDissolve 2.75 g of ceric ammonium nitrate in 1 N nitric acid to obtain 100 mL of solution, and filter. Standardize the solution as follows.Accurately measure 10 mL of freshly standardized 0.1 N ferrous ammonium sulfate VS into a flask, and dilute with water to about 100 mL. Add 1 drop of nitrophenanthroline TS, and titrate with the ceric ammonium nitrate solution to a colorless endpoint.Ceric Sulfate, Tenth-Normal (0.1 N )Ce(SO 4)2, 332.2433.22 g in 1000 mLUse commercially available volumetric standard solution. Standardize the solution as follows. Accurately weigh about 0.2 g of sodium oxalate, primary standard, dried according to theinstructions on its label, and dissolve in 75 mL of water. Add, with stirring, 2 mL of sulfuric acid that has previously been mixed with 5 mL of water, mix well, add 10 mL of hydrochloric acid, and heat to between 70 and 75. Titrate with 0.1 N ceric sulfate to a permanent slight yellow color. Each 6.700 mg of sodium oxalate is equivalent to 1 mL of 0.1 N ceric sulfate.Cupric Nitrate, Tenth-Normal (0.1 N)Cu(NO 3)2·2.5H 2O, 232.5923.26 g in 1000 mLCu(NO 3)2·3H 2O, 241.60 24.16 g in 1000 mLDissolve 23.3 g of cupric nitrate 2.5 hydrate, or 24.2 g of the trihydrate, in water to make 1000 mL. Standardize the solution as follows.Transfer 20.0 mL of the solution to a 250-mL beaker. Add 2 mL of 5 M sodium nitrate, 20 mL of ammonium acetate TS, and sufficient water to make 100 mL. Titrate with 0.05 M edetate disodium VS. Determine the endpoint potentiometrically using a cupric ion-double junctionreference electrode system. Perform a blank determination, and make any necessary correction.Standard Dichlorophenol–Indophenol SolutionTo 50 mg of 2,6-dichlorophenol–indophenol sodium that has been stored in a desiccator over soda lime add 50 mL of water containing 42 mg of sodium bicarbonate, shake vigorously, and when the dye is dissolved, add water to make 200 mL. Filter into an amber, glass-stoppered bottle. Use within 3 days and standardize immediately before use. Standardize the solution as follows. Accurately weigh 50 mg of USP Ascorbic Acid RS , and transfer to a glass-stoppered, 50-mLvolumetric flask with the aid of a sufficient volume of metaphosphoric–acetic acids TS to make 50 mL. Immediately transfer 2 mL of the ascorbic acid solution to a 50-mL conical flask containing 5 mL of the metaphosphoric–acetic acids TS, and titrate rapidly with the dichlorophenol–indophenol solution until a distinct rose-pink color persists for at least 5 seconds. Perform a blank titration by titrating 7 mL of the metaphosphoric–acetic acids TS plus a volume of water equal to the volume of the dichlorophenol solution used in titrating the ascorbic acid solution. Express theconcentration of the standard solution in terms of its equivalent in mg of ascorbic acid.Edetate Disodium, Twentieth-Molar (0.05 M )C 10H 14N 2Na 2O 8·2H 2O, 372.2418.61 g in 1000 mLDissolve 18.6 g of edetate disodium in water to make 1000 mL, and standardize the solution as follows.Accurately weigh about 200 mg of chelometric standard calcium carbonate, previously dried at 110 for 2 hours and cooled in a desiccator, transfer to a 400-mL beaker, add 10 mL of water, and swirl to form a slurry. Cover the beaker with a watch glass, and introduce 2 mL of dilutedhydrochloric acid from a pipet inserted between the lip of the beaker and the edge of the watch glass. Swirl the contents of the beaker to dissolve the calcium carbonate. Wash down the sides of the beaker, the outer surface of the pipet, and the watch glass with water, and dilute with water to about 100 mL. While stirring the solution, preferably with a magnetic stirrer, add about 30 mL of the edetate disodium solution from a 50-mL buret. Add 15 mL of sodium hydroxide TS and 300 mg of hydroxy naphthol blue, and continue the titration with the edetate disodium solution to a blue endpoint.Ferric Ammonium Sulfate, Tenth-Normal (0.1 N)FeNH 4(SO 4)2·12H 2O, 482.19 48.22 g in 1000 mLDissolve 50 g of ferric ammonium sulfate in a mixture of 300 mL of water and 6 mL of sulfuric acid, dilute with water to 1000 mL, and mix. Standardize the solution as follows.Accurately measure about 40 mL of the solution into a glass-stoppered flask, add 5 mL ofhydrochloric acid, mix, and add a solution of 3 g of potassium iodide in 10 mL of water. Insert the stopper, allow to stand for 10 minutes, then titrate the liberated iodine with 0.1 N sodiumthiosulfate VS, adding 3 mL of starch TS as the endpoint is approached. Correct for a blank run on the same quantities of the same reagents.Store in tight containers, protected from light.Ferrous Ammonium Sulfate, Tenth-Normal (0.1 N)Fe(NH 4)2(SO 4)2·6H 2O, 392.1439.21 g in 1000 mLDissolve 40 g of ferrous ammonium sulfate in a previously cooled mixture of 40 mL of sulfuric acid and 200 mL of water, dilute with water to 1000 mL, and mix. On the day of use, standardize the solution as follows.Accurately measure 25 to 30 mL of the solution into a flask, add 2 drops of orthophenanthroline TS, and titrate with 0.1 N ceric sulfate VS until the red color is changed to pale blue.Hydrochloric Acid, Normal (1 N)HCl, 36.4636.46 g in 1000 mLDilute 85 mL of hydrochloric acid with water to 1000 mL. Standardize the solution as follows.Accurately weigh about 5.0 g of tromethamine, dried according to the label instructions. Dissolve in 50 mL of water, and add 2 drops of bromocresol green TS. Titrate with 1 N hydrochloric acid to a pale yellow endpoint. Each 121.14 mg of tromethamine is equivalent to 1 mL of 1 N hydrochloric acid.Hydrochloric Acid, Half-Normal (0.5 N)HCl, 36.4618.23 g in 1000 mLTo a 1000-mL volumetric flask containing 40 mL of water slowly add 43 mL of hydrochloric acid. Cool, and add water to volume. Standardize the solution as follows.Accurately weigh about 2.5 g of tromethamine, dried according to the label instructions. Proceed as directed under Hydrochloric Acid, Normal (1 N), beginning with “Dissolve in 50 mL of water.”Hydrochloric Acid, Half-Normal (0.5 N) in MethanolHCl, 36.4618.23 g in 1000 mLTo a 1000-mL volumetric flask containing 40 mL of water slowly add 43 mL of hydrochloric acid. Cool, and add methanol to volume. Standardize the solution as follows.Accurately weigh about 2.5 g of tromethamine, dried according to the label instructions. Proceed as directed under Hydrochloric Acid, Normal (1 N), beginning with “Dissolve in 50 mL of water.”Hydrochloric Acid, Alcoholic, Tenth-Molar (0.1 M)HCl, 36.46Dilute 9.0 mL of hydrochloric acid to 1000 mL with aldehyde–free alcohol.Iodine, Tenth-Normal (0.1 N)I, 126.9012.69 g in 1000 mLDissolve about 14 g of iodine in a solution of 36 g of potassium iodide in 100 mL of water, add 3 drops of hydrochloric acid, dilute with water to 1000 mL, and standardize the solution as follows. Transfer 25.0 mL of the iodine solution to a 250-mL flask, dilute with water to 100 mL, add 1 mL of 1 N hydrochloric acid, swirl gently to mix, and titrate with 0.1 N sodium thiosulfate VS until the solution has a pale yellow color. Add 2 mL of starch TS and continue titrating until the solution is colorless.Preserve in amber-colored, glass-stoppered bottles.Iodine, Twentieth-Normal (0.05 N)I, 126.906.33 g in 1000 mLDissolve about 6.5 g of iodine in a solution of 18 g of potassium iodide in 100 mL of water, add 3 drops of hydrochloric acid, dilute with water to 1000 mL, and standardize the solution as follows. Transfer 50.0 mL of the iodine solution to a 250-mL flask, dilute with water to 100 mL, add 1 mL of 1 N hydrochloric acid, swirl gently to mix, and titrate with 0.1 N sodium thiosulfate VS until the solution has a pale yellow color. Add 2 mL of starch TS, and continue titrating until the solution is colorless.Iodine, Hundredth-Normal (0.01 N)I, 126.901.269 g in 1000 mLDissolve about 1.4 g of iodine in a solution of 3.6 g of potassium iodide in 100 mL of water, add 3 drops of hydrochloric acid, dilute with water to 1000 mL, and standardize the solution as follows. Transfer 100.0 mL of iodine solution to a 250-mL flask, add 1 mL of 1 N hydrochloric acid, swirl gently to mix, and titrate with 0.1 N sodium thiosulfate VS until the solution has a pale yellow color. Add 2 mL of starch TS, and continue titrating until the solution is colorless.Preserve in amber-colored, glass-stoppered bottles.Lead Nitrate, Hundredth-Molar (0.01 M)Pb (NO 3)2, 331.213.312 g in 1000 mLXylenol Orange Triturate— Triturate 1 part of xylenol orange with 99 parts of potassium nitrate. 0.1 M Lead Nitrate— Dissolve 33 g of lead nitrate in 1000 mL of water. Standardize the solution as follows. To 20.0 mL of the lead nitrate solution add 300 mL of water. Add about 50 mg ofXylenol Orange Triturate, and add methenamine until the solution becomes violet-pink. Titrate with 0.1 M edetate disodium VS to the yellow endpoint. Calculate the molarity.Dilute 50.0 mL of 0.1 M Lead Nitrate to 500.0 mL with water.Lead Perchlorate, Tenth-Molar (0.1 M)Pb(ClO 4)2·3H 2O, 460.1546.01 g in 1000 mLDissolve 46 g of lead perchlorate in water, and dilute with water to 1000.0 mL. Accurately weigh about 150 mg of sodium sulfate, previously dried at 105 for 4 hours, and dissolve in 50 mL of water. Add 50 mL of a mixture of water and formaldehyde (1:1), and stir for about 1 minute. Determine the endpoint potentiometrically using a lead ion selective electrode. Perform a blank determination, and make any necessary corrections. Each 14.204 mg of sodium sulfate is equivalent to 1 mL of 0.1 M lead perchlorate.Lead Perchlorate, Hundredth-Molar (0.01 M)Pb(ClO 4)2, 406.10Accurately pipet 100 mL of commercially available 0.1 M lead perchlorate solution into a 1000-mL volumetric flask, add a sufficient quantity of water to make 1000 mL, and standardize the solution as follows.Accurately pipet 50 mL of 0.01 M lead perchlorate solution, as prepared above, into a 250-mL conical flask. Add 3 mL of aqueous hexamethylenetetramine solution (2.0 g per 100 mL) and 4 drops of 0.5% xylenol orange indicator prepared by adding 500 mg of xylenol orange to 10 mL ofalcohol and diluting with water to 100 mL. (Omit the alcohol if the sodium salt of the indicator is used). Titrate with 0.05 M edetate disodium VS to a yellow endpoint.Lithium Methoxide, Fiftieth-Normal (0.02 N) in MethanolLiO, 37.97CH3759.6 mg in 1000 mLDissolve 0.12 g of freshly cut lithium metal in 150 mL of methanol, cooling the flask during addition of the metal. When the reaction is complete, add 850 mL of methanol, and mix. Store the solution preferably in the reservoir of an automatic delivery buret suitably protected from carbon dioxide and moisture. Standardize the solution by titration against benzoic acid as described under Sodium Methoxide, Tenth-Normal (0.1 N) (in Toluene), but use only 100 mg of benzoic acid. Each 2.442 mg of benzoic acid is equivalent to 1 mL of 0.02 N lithium methoxide.[N OTE—Restandardize the solution frequently. ]Lithium Methoxide, Tenth-Normal (0.1 N) in ChlorobenzeneOLi, 37.97CH33.798 g in 1000 mLDissolve 700 mg of freshly cut lithium metal in 150 mL of methanol, cooling the flask during addition of the metal. When the reaction is complete, add 850 mL of chlorobenzene. If cloudiness or precipitation occurs, add sufficient methanol to clarify the solution. Store preferably in the reservoir of an automatic delivery buret suitably protected from carbon dioxide and moisture. Standardize the solution by titration against benzoic acid as described under Sodium Methoxide, Tenth-Normal (0.1 N) (in Toluene).[N OTE—Restandardize the solution frequently. ]Lithium Methoxide, Tenth-Normal (0.1 N) in MethanolOLi, 37.97CH33.798 g in 1000 mLDissolve 700 mg of freshly cut lithium metal in 150 mL of methanol, cooling the flask during addition of the metal. When the reaction is complete, add 850 mL of methanol. If cloudiness or precipitation occurs, add sufficient methanol to clarify the solution. Store preferably in the reservoir of an automatic delivery buret suitably protected from carbon dioxide and moisture. Standardize the solution by titration against benzoic acid as described under Sodium Methoxide, Tenth-Normal (0.1 N) (in Toluene).[N OTE—Restandardize the solution frequently. ]Lithium Methoxide, Tenth-Normal (0.1 N) in TolueneCH 3OLi, 37.973.798 g in 1000 mLDissolve 700 mg of freshly cut lithium metal in 150 mL of methanol, cooling the flask during addition of the metal. When reaction is complete, add 850 mL of toluene. If cloudiness or precipitation occurs, add sufficient methanol to clarify the solution. Store preferably in the reservoir of an automatic delivery buret suitably protected from carbon dioxide and moisture. Standardize the solution by titration against benzoic acid as described under Sodium Methoxide, Tenth-Normal (0.1 N) (in Toluene).[N OTE —Restandardize the solution frequently. ]Magnesium Chloride, 0.01 MMgCl 2·6H 2O, 203.302.0330 g in 1000 mLDissolve about 2.04 g of magnesium chloride in 1000 mL of freshly boiled and cooled water, and standardize the solution as follows.Accurately measure 25 mL of the prepared magnesium chloride solution. Add 50 mL of water, 3 mL of ammonia–ammonium chloride buffer TS and 0.04 g of eriochrome black T–sodium chloride reagent. Titrate with 0.05 M edetate disodium VS until the red-purple color of the solution changes to blue-purple.Mercuric Nitrate, Tenth-Molar (0.1 M )Hg(NO 3)2, 324.6032.46 g in 1000 mLDissolve about 35 g of mercuric nitrate in a mixture of 5 mL of nitric acid and 500 mL of water, and dilute with water to 1000 mL. Standardize the solution as follows.Transfer an accurately measured volume of about 20 mL of the solution to a conical flask, and add 2 mL of nitric acid and 2 mL of ferric ammonium sulfate TS. Cool to below 20, and titrate with 0.1 N ammonium thiocyanate VS to the first appearance of a permanent brownish color.Oxalic Acid, Tenth-Normal (0.1 N)H 2C 2O 4·2H 2O, 126.07 6.303 g in 1000 mLDissolve 6.45 g of oxalic acid in water to make 1000 mL. Standardize by titration against freshly standardized 0.1 N potassium permanganate VS as directed under Potassium Permanganate, Tenth-Normal (0.1 N).Preserve in glass-stoppered bottles, protected from light.Perchloric Acid, Tenth-Normal (0.1 N) in DioxaneMix 8.5 mL of perchloric acid with sufficient dioxane to make 1000 mL. Standardize the solution as follows.Accurately weigh about 700 mg of potassium biphthalate, previously crushed lightly and dried at 120 for 2 hours, and dissolve in 50 mL of glacial acetic acid in a 250-mL flask. Add 2 drops of crystal violet TS, and titrate with the perchloric acid solution until the violet color changes to bluish green. Carry out a blank determination. Each 20.423 mg of potassium biphthalate is equivalent to 1 mL of 0.1 N perchloric acid.Perchloric Acid, Tenth-Normal (0.1 N) in Glacial Acetic AcidHClO, 100.46410.05 g in 1000 mL[N OTE—Where called for in the tests and assays, this volumetric solution is specified as “0.1 N perchloric acid.” Thus, where 0.1 N or other strength of this volumetric solution is specified, the solution in glacial acetic acid is to be used, unless the words “in dioxane” are stated. [See also Perchloric Acid, Tenth-Normal (0.1 N) in Dioxane.] ]Mix 8.5 mL of perchloric acid with 500 mL of glacial acetic acid and 21 mL of acetic anhydride, cool, and add glacial acetic acid to make 1000 mL. Alternatively, the solution may be prepared as follows. Mix 11 mL of 60 percent perchloric acid with 500 mL of glacial acetic acid and 30 mL of acetic anhydride, cool, and add glacial acetic acid to make 1000 mL.Allow the prepared solution to stand for 1 day for the excess acetic anhydride to be combined, and determine the water content by Method I (see Water Determination 921), except to use a test specimen of about 5 g of the 0.1 N perchloric acid that is expected to contain approximately 1 mg of water and the Reagent (see Reagent under Method Ia in Water Determination 921) diluted such that 1 mL is equivalent to about 1 to 2 mg of water. If the water content exceeds 0.5%, add more acetic anhydride. If the solution contains no titratable water, add sufficient water to obtain a content of between 0.02% and 0.5% of water. Allow the solution to stand for 1 day, and again titrate the water content. The solution so obtained contains between 0.02% and 0.5% of water, indicating freedom from acetic anhydride.Standardize the solution as follows.Accurately weigh about 700 mg of potassium biphthalate, previously crushed lightly and dried at 120 for 2 hours, and dissolve it in 50 mL of glacial acetic acid in a 250-mL flask. Add 2 drops of crystal violet TS, and titrate with the perchloric acid solution until the violet color changes to blue-green. Deduct the volume of the perchloric acid consumed by 50 mL of the glacial acetic acid. Each 20.423 mg of potassium biphthalate is equivalent to 1 mL of 0.1 N perchloric acid.Potassium Arsenite, Tenth-Normal (0.1 N)KAsO2, 146.027.301 g in 1000 mLDissolve 4.9455 g of arsenic trioxide primary standard, previously dried at 105 for 1 hour, in 75 mL of 1 N potassium hydroxide. Add 40 g of potassium bicarbonate, dissolved in about 200 mL of water, and dilute with water to 1000.0 mL.Potassium Bromate, Tenth-Normal (0.1 N)KBrO3, 167.002.784 g in 1000 mLDissolve 2.784 g of potassium bromate in water to make 1000 mL, and standardize the solution as follows.Transfer an accurately measured volume of about 40 mL of the solution to a glass-stoppered flask, add 3 g of potassium iodide, and follow with 3 mL of hydrochloric acid. Allow to stand for 5 minutes, then titrate the liberated iodine with 0.1 N sodium thiosulfate VS, adding 3 mL of starch TS as the endpoint is approached. Correct for a blank run on the same quantities of the same reagents, and calculate the normality.Potassium Bromide–Bromate, Tenth-Normal (0.1 N)Dissolve 2.78 g of potassium bromate (KBrO3) and 12.0 g of potassium bromide (KBr) in water, and dilute with water to 1000 mL. Standardize by the procedure set forth for Potassium Bromate, Tenth-Normal (0.1 N).Potassium Dichromate, Tenth-Normal (0.1 N)K 2Cr2O7, 294.184.903 g in 1000 mLDissolve about 5 g of potassium dichromate in 1000 mL of water. Standardize the solution as follows.Transfer 25.0 mL of this solution to a glass-stoppered, 500-mL flask, add 2 g of potassium iodide (free from iodate), dilute with 200 mL of water, add 5 mL of hydrochloric acid, allow to stand for 10 minutes in a dark place, and titrate the liberated iodine with 0.1 N sodium thiosulfate VS, adding 3 mL of starch TS as the endpoint is approached. Carry out a blank determination.Potassium Ferricyanide, Twentieth-Molar (0.05 M)K 3Fe(CN)6, 329.2416.46 g in 1000 mLDissolve about 17 g of potassium ferricyanide in water to make 1000 mL. Standardize the solution as follows.Transfer 50.0 mL of this solution to a glass-stoppered, 500-mL flask, dilute with 50 mL of water, add 10 mL of potassium iodide TS and 10 mL of dilute hydrochloric acid, and allow to stand for 1 minute. Then add 15 mL of zinc sulfate solution (1 in 10), and titrate the liberated iodine with 0.1 N sodium thiosulfate VS, adding 3 mL of starch TS as the endpoint is approached.Protect from light, and restandardize before use.Potassium Hydroxide, Normal (1 N)KOH, 56.1156.11 g in 1000 mLDissolve 68 g of potassium hydroxide in about 950 mL of water. Add a freshly prepared saturated solution of barium hydroxide until no more precipitate forms. Shake the mixture thoroughly, and allow it to stand overnight in a stoppered bottle. Decant the clear liquid, or filter the solution in a tight, polyolefin bottle, and standardize by the procedure set forth for Sodium Hydroxide, Normal (1 N).Potassium Hydroxide, Alcoholic, Half-Normal (0.5 N)28.06 g in 1000 mLDissolve about 34 g of potassium hydroxide in 20 mL of water, and add aldehyde-free alcohol to make 1000 mL. Allow the solution to stand in a tightly stoppered bottle for 24 hours. Then quickly decant the clear supernatant into a suitable, tight container, and standardize the solution as follows.Accurately measure about 25 mL of 0.5 N hydrochloric acid VS. Dilute with 50 mL of water, add 2 drops of phenolphthalein TS, and titrate with the alcoholic potassium hydroxide solution until a permanent, pale pink color is produced.[N OTE—Store in tightly stoppered bottles, protected from light. ]Potassium Hydroxide, Alcoholic, Tenth-Molar (0.1 M)。

美国药典－中英文对照译文美国药典中记载的辣椒碱资料辣椒碱（辣椒素）分子结构式：C18H27NO3，分子量：305.41，化学名：（反）－N－[（4－N－羟基－3－甲氧基苯基）－甲基]－8－甲基－6－壬烯基酰胺以干燥提取物计算，辣椒碱含辣椒二萜类化合物总量为标示量的90％－100%,其中辣椒素的含量达到50％以上，辣椒素和二氢辣椒素总量超过75％，其它辣椒素类化合物总量不足15％。

注意事项：小心处置辣椒碱，谨防吸入辣椒碱微粒，勿使身体接触辣椒碱。

包装贮藏：密封包装，置避光，阴凉处保存。

标示量：以辣椒二萜类化合物总百分含量表示。

美国药典参考标准：美国药典辣椒素标准规范，美国药典二氢辣椒素标准规范。

鉴别：配制1.0mg/ml辣椒碱甲醇溶液，配制符合美国药典标准的辣椒碱1.0mg/ml甲醇溶液作为对照液，分别点样于0.25mm厚硅胶、凝胶混合薄层板上，点样量为10礚，将薄层板放于乙醚－甲醇（19:1）展开剂中展开，待展开剂前沿至薄层板3/4处时将薄层板取出，晾干，用0.5% 2,6-二溴苯醌-氯化亚胺甲醇溶液喷雾显色，放于氨气中片刻，取出，鉴别色谱图：供试液主要斑点颜色（兰色）及R值与对照液主要斑点颜色（兰色）及R值一致。

熔点〈741〉: 57°－66°, 一般熔融起始温度至结束温度温差不超过5°。

干燥失重〈731〉: 置40°P2O5真空干燥器中干燥5小时，失重不超过1.0%。

灼烧残渣：≤1.0％。

辣椒素，二氢辣椒素及其它辣椒二萜类化合物含量测定：流动相：磷酸水溶液（l ：1000，V/V）：乙腈(600:400)混匀，0.5祄微孔滤膜滤过，脱气。

流动相视色谱行为可作适当调整。

辣椒素对照液：精密称取美国药典标准的辣椒碱适量溶于甲醇中，配制约0.1 mg/mL的辣椒甲醇溶液。

二氢辣椒素对照液：精密称取美国药典标准的辣椒碱适量溶于甲醇中，配制约0.025mg/mL的辣椒甲醇溶液。

<791>pH对于药典用途，pH定义为由合适的，正确标定的，使用对氢离子活度敏感的指示电极，玻璃电极，及适当的参比电极，具有重复pH值至0.02单位的电位计或酸度计(pH 计)给定的值。

仪器应能够指示通过电极对的电势，对于pH标定，通过操纵“标定”，“调零”，“不对称”或“校正”控制调节电路的电势，并应可以通过“温度”和“斜率”控制来控制每单位毫伏的变化改变pH读数。

除了在单个专论中有特殊说明的外，测量在25 ± 2℃下进行。

pH值由以下方程式定义：pH = pHs + (E – E S)/k其中E 和 E S分别是检测中原电池所包含溶液测定的电势，由pH表示，及合适的标定缓冲溶液，用pHs表示。

K值是每单位pH 值的改变所对应改变的电势，理论上在任何温度t下它都应为[0.05916 + 0.000198(t – 25℃)]伏。

需要强调的是pH定义，pH尺度和标准缓冲液的指定值都是为了确定一个实际的，可操作的操作系统，以便在实验室间进行结果对比。

因此测定的pH值与根据定义pH =–log a H+计算出的pH值并不精确符合。

只要被测溶液与标准缓冲液中的成分充分接近，测定的pH值就与理论pH值十分接近了。

尽管没有关于测量氢离子活度或浓度的系统适应性要求的制定，在水溶液中得到的值仍与相应的氢离子活度相近。

如果通过用标准缓冲液校正pH计，然后用该pH计来测量非水溶液或悬浮溶液的“pH”值，酸碱的电离常量，溶剂的介电常数，液接界电势（可能有近似1单位pH 的误差）和玻璃电极氢离子响应值都发生改变。

基于这些原因，性状为部分水溶液的溶液得到的pH值只是一个表观pH值。

pH计标定用的缓冲溶液标准缓冲溶液的制备描述如附表*所述。

必需纯度的缓冲盐可通过国家科学院（National Institute of Science and Technology）得到。

溶液应贮藏在带有密封装置的或有二氧化碳吸收管（苏打石灰）的硬质玻璃瓶或聚乙烯瓶中。

Aspirin(USP 34)Aspirin contains not less than 99.5 percent and not more than 100.5 percent ofC9H8O4.calculated on the dried basis.根据干燥品计算，本品C9H8O4为标示量的99.5%~100.5%。

Packaging and storage -Preserve in the tight containers.包装与贮藏-贮藏于封闭的容器中。

USP REFERENCE STANDRANDS<11>-USP Aspirin RSUSP 标准物质-USP 阿司匹林对照品Identification-A: Heat it with water for minutes,cool,and add 1 or 2 drops ferric chloride TS: a violed-red color is produced.鉴别-1.水浴加热数分钟，冷却，加入1到2滴FeCl3 试液，测得颜色为紫红色。

B: Infrared AbsorptionLoss on Drying-Dry it over silica gel for 5 hours: it loses not more than 0.5% of its weight.干燥失重-硅胶干燥器中干燥5小时，减少重量不得超过0.5%。

Readily carbonizable substances-Dissolve 500mg in 5ml of sulfuric acid: the solution has no more color than matching fluid Q.易碳化物-取500mg本品溶于5ml硫酸溶液中，溶液颜色不得深于标准溶液Q。

Residue on Ignition: not more than 0.05%.炙灼残渣-不得超过0.05%。