Tubastatin_A_Hydrochloride_HNMR_05415_MedChemExpress

盐酸阿考替胺及制剂一、化合物大体信息英文名AcotiamideHydrochloride HydrateAcotiamidehydrochlorideAcotiamide产品名称阿考替胺盐酸盐三水合物阿考替胺盐酸盐阿考替胺分子结构分子式分子量CAS 登录号773092-05-0二、产品信息【药品名称】盐酸阿考替胺【英文名称】acotiamide hydrochloride hydrate【商品名】Acofide【中文化学名】：N-[2-(二异丙基氨基)乙基]-2-[(2-羟基-4,5-二甲氧基苯甲酰)氨基]-1,3-噻唑-4-羧酸胺盐酸盐三水合物【英文化学名】：N-{2-[Bis(1-methylethyl)amino]ethyl}-2-[(2-hydroxy-4,5-dimethoxybenzoyl)amino]thiazole-4-carboxamidemonohydrochloride trihydrate【化学结构】：【分子式】：【分子量】：【CAS】：773092-05-0【性状】白色或类白色结晶性粉末【熔点】154℃-156℃【溶解度】本品在DMF中溶解，甲醇中略溶，乙醇和水中微溶，丙酮中极微溶，乙酸乙酯中不溶。

【pka】[药理作用及特点] 阿考替胺最先由日本Zeria新药工业株式会社研发，后由Astellas 制药与Zeria药业在日本一路推出。

阿考替胺口服片剂在消化道主如果通过抑制乙酰胆碱酯的机制起作用，可增进胃动力、改善胃容纳障碍、增强胃底扩张。

最新数据显示，西方国家普通人群消化不良症状已接近40%，并显著降低了生活质量。

其中小部份人群由胃溃疡引发，可通过根治幽门螺杆菌进行医治，约20%的有症状人群属于胃食道逆流疾病，可通过质子泵抑制剂有效医治，但大多数消化不良人群属于FD，对于FD的医治目前仍具有挑战性。

【注册分类】化药3+3类【剂型规格】100mg【制剂】片剂【适应症】用于医治功能性消化不良（FD）【用法用量】一天三次，一次100mg，饭前服用。

利培酮 risperidone
阿立哌唑 aripiprazole
齐拉西酮 ziprasidone
代表药物
用于急性和慢性精神分裂症。 代谢物9-羟基-利培酮作用与 本品相似。
第三代非典型抗精神病 药物，用于精神分裂症。
为非典型抗精神病药，构造 与吩噻嗪类或丁酞苯类不同。 能抑制突触对5-羟色胺和去 甲肾上腺素的再摄取。
盐酸氯丙嗪——不良反响
会引起结节-漏斗通路和黑质-纹状体通路的阻断，导致内 分泌作用血液中的催乳素增高，促皮质素减少，垂体生长 素减少以及锥体外系综合症导致的运动不能、静坐不能、 肌肉张力障碍等问题。
同时阻断α受体和M受体，引起体位性低血压、体温下降 和口干、便秘、视力模糊等不良反响。
本品药后应静卧1~2小时，血压过低者可静脉滴注去甲肾 上腺素，禁用肾上腺素。长期大量应用本品可出现锥体外 系反响和内分泌紊乱等。
不良反响：锥体外系反响较常见，有致畸作用 用药注意：剂量个体化，长期用药者应注意观察
迟发性运动障碍的早期病症，制止突然停药，以 免出现迟发性运动障碍。 本品可致畸，并可从乳汁中分泌，孕妇及哺乳 期妇女禁用。
二苯丁基哌啶类
对丁酰苯类抗精神病药物的构造改造过程中得到二 苯丁基哌啶类抗精神病药物
氟哌啶醇〔haloperidol〕是本类最早应用于 临床的药物。
丁酰苯类——构效关系
氟哌啶醇〔haloperidol〕
化学名为1-〔4-氟苯基〕-4-[4-〔4-氯苯基〕-4-羟基-1-哌啶基]-1-丁酮 〔4-[ 4(4-chlorophenyl)- 4-hydroxy-1-piperidinyl]-1-(4-fluorophenyl)-1-butanone〕 ，又名氟哌啶苯，卤吡醇。

1. IDENTIFICATION OF THE SUBSTANCE/TREPARATION AND THE COMPANY/UNDERTAKING3.HAZARDS IDENTIFICATION4. FIRST AID MEASURESMATERIAL SAFETY DATA SHEETProduct name:Supplier:Tel:EMERGENCY OVERVIEW: May cause skin irritation and/or dermatitisPrinciple routes of exposure: Inhalation: Ingestion: Skin contact: Eye contact:SkinMay cause irritation of respiratory tract May be harmful if swallowed May cause allergic skin reaction Avoid contact with eyesStatements of hazard MAY CAUSE ALLERGIC SKIN REACTION.Statements of Spill of Leak Label Eliminate all ignition sources. Absorb and/or contain spill with inert materials (e.g., sand, vermiculite). Then place in appropriate container. For large spills, use water spray to disperse vapors, flush spill area. Prevent runoff from entering waterways or sewers.General advice:POSITION/INFORMATION ON INGREDIENTSInhalation:Skin contact:Ingestion:Eye contact:Protection of first – aiders:Medical conditions aggravated by exposure: In the case of accident or if you fell unwell, seek medical advice immediately (show the label where possible).Move to fresh air, call a physician immediately.Rinse immediately with plenty of water and seek medical adviceDo not induce vomiting without medical advice.In the case of contact with eyes, rinse immediately with plenty of water and seek medical advice.No information availableNone knownSuitable extinguishing media:Specific hazards:Special protective equipment for firefighters:Flash point:Autoignition temperature:NFPA rating Use dry chemical, CO2, water spray or “alcohol” foam Burning produces irritant fumes.As in any fire, wear self-contained breathing apparatus pressure-demand, MSHA/NIOSH (approved or equivalent) and full protective gearNot determinedNot determinedNFPA Health: 1 NFPA Flammability: 1 NFPA Reactivity: 0Personal precautions: Environmental precautions: Methods for cleaning up: Use personal protective equipment.Prevent product from entering drains.Sweep up and shovel into suitable containers for disposalStorage:7. HANDLING AND STORAGE5.FIRE-FIGHTING MEASURES6. ACCIDENTAL RELEASE MEASURESRoom temperature Handling:Safe handling advice: Incompatible products:Use only in area provided with appropriate exhaust ventilation.Wear personal protective equipment.Oxidising and spontaneously flammable productsEngineering measures: Respiratory protection: Skin and body protection:Eye protection: Hand protection: Hygiene measures:Ensure adequate ventilation.Breathing apparatus only if aerosol or dust is formed. Usual safety precautions while handling the product will provide adequate protection against this potential effect. Safety glasses with side-shieldsPVC or other plastic material glovesHandle in accordance with good industrial hygiene and safety practice.Melting point/range: Boiling point/range: Density: Vapor pressure: Evaporation rate: Vapor density: Solubility (in water): Flash point:Autoignition temperature:No Data available at this time. No Data available at this time. No data available No data available No data available No data available No data available Not determined Not determinedStability: Stable under recommended storage conditions. Polymerization: None under normal processing.Hazardous decomposition products: Thermal decomposition can lead to release of irritating gases and vapours such as carbon oxides.Materials to avoid: Strong oxidising agents.10. STABILITY AND REACTIVITY9. PHYSICAL AND CHEMICAL PROPERTIES8. EXPOSURE CONTROLS/PERSONAL PROTECTION11. TOXICOLOGICAL INFORMATIONConditions to avoid: Exposure to air or moisture over prolonged periods.Product information Acute toxicityChronic toxicity:Local effects: Chronic exposure may cause nausea and vomiting, higher exposure causes unconsciousness.Symptoms of overexposure may be headache, dizziness, tiredness, nausea and vomiting.Specific effects:May include moderate to severe erythema (redness) and moderate edema (raised skin), nausea, vomiting,headache.Primary irritation: Carcingenic effects: Mutagenic effects: Reproductive toxicity:No data is available on the product itself. No data is available on the product itself. No data is available on the product itself. No data is available on the product itself.Mobility:Bioaccumulation: Ecotoxicity effects: Aquatic toxicity:No data available No data available No data availableMay cause long-term adverse effects in the aquatic environment.12. ECOLOGICAL INFORMATION13. DISPOSAL CONSIDERATIONSWaste from residues/unused products:Contaminated packaging:Waste disposal must be in accordance with appropriate Federal, State and local regulations. This product, if unaltered by use, may be disposed of treatment at a permitted facility or as advised by your local hazardous waste regulatory authority. Residue from fires extinguished with this material may be hazardous.Do not re-use empty containers.UN/Id No:Not regulated14. TRANSPORT INFFORMATIONDOTProper shipping name: Not regulatedTGD(Canada)WHMIS hazard class: Non - controlledIMDG/IMOIMDG – Hazard Classifications Not ApplicableIMO – labels:15. REGULATORY INFOTMATION International Inventories16. OTHER INFORMATIONPrepared by: Health & SafetyDisclaimer: The information and recommendations contained herein are based upon tests believed to be reliable.However, XABC does not guarantee the accuracy or completeness NOR SHALL ANY OF THIS INFORMATION CONSTITUTE A WARRANTY, WHETHER EXPRESSED OR IMPLIED, AS TO THE SAFETY OF THE GOOD, THE MERCHANTABILITY OF THE GOODS, OR THE FITNESS OF THE FITNESS OF THE GOODS FOR A PARTICULAR PURPOSE. Adjustment to conform to actual conditions of usage maybe required. XABC assumes no responsibility for results obtained or for incidental or consequential damages, including lost profits arising from the use of these data. No warranty against infringement of any patent, copyright or trademark is made or implied.End of safety data sheet。

4.1.3.Buffer solutions EUROPEAN PHARMACOPOEIA8.0Sulfite standard solution (1.5ppm SO 2).5002900.Dissolve sodium metabisulfite R equivalent to 0.152g of Na 2S 2O 5in water R and dilute to 100.0mL with the same solvent.Dilute 5.0mL of this solution to 100.0mL with water R .To 3.0mL of the resulting solution,add 4.0mL of 0.1M sodium hydroxide and dilute to 100.0mL with water R .Thallium standard solution (10ppm Tl).5003000.Dissolve thallous sulfate R equivalent to 0.1235g of Tl 2SO 4in a 9g/L solution of sodium chloride R and dilute to 1000.0mL with the same solution.Dilute 10.0mL of the solution to 100.0mL with the 9g/L solution of sodium chloride R .Tin liposoluble standard solution (1000ppm Sn).5005000.A tin (metal)organic compound in an oil.Tin standard solution (5ppm Sn).5003100.Dissolve tin R equivalent to 0.500g of Sn in a mixture of 5mL of water R and 25mL of hydrochloric acid R and dilute to1000.0mL with water R .Dilute the solution to 100times itsvolume with a 2.5per cent V/V solution of hydrochloric acid R immediately before use.Tin standard solution (0.1ppm Sn).5003101.Immediately before use,dilute tin standard solution (5ppmSn)R to 50times its volume with water R .Titanium standard solution (100ppm Ti).5003200.Dissolve 100.0mg of titanium R in 100mL of hydrochloricacid R diluted to 150mL with water R ,heating if necessary.Allow to cool and dilute to 1000mL with water R .Vanadium standard solution (1g/L V).5003300.Dissolve in water R ammonium vanadate R equivalent to0.230g of NH 4VO 3and dilute to 100.0mL with the samesolvent.Zinc standard solution (5mg/mL Zn).5003400.Dissolve 3.15g of zinc oxide R in 15mL of hydrochloric acid Rand dilute to 500.0mL with water R .Zinc standard solution (100ppm Zn).5003401.Immediately before use,dilute with water R to 10times its volume a solution containing zinc sulfate R equivalent to0.440g of ZnSO 4,7H 2O and 1mL of acetic acid R in 100.0mL.Zinc standard solution (10ppm Zn).5003402.Immediately before use,dilute zinc standard solution (100ppm Zn)R to 10times its volume with water R .Zinc standard solution (5ppm Zn).5003403.Immediately before use,dilute zinc standard solution (100ppm Zn)R to 20times its volume with water R .Zirconium standard solution (1g/L Zr).5003500.Dissolve zirconyl nitrate R equivalent to 0.293g ofZrO(NO 3)2,2H 2O in a mixture of 2volumes of hydrochloric acid R and 8volumes of water R and dilute to 100.0mL with the same mixture of solvents.01/2014:401034.1.3.BUFFER SOLUTIONSBuffered acetone solution.4000100.Dissolve 8.15g of sodium acetate R and 42g of sodium chloride R in water R ,add 68mL of 0.1M hydrochloric acid and 150mL of acetone R and dilute to 500mL with water R .Buffer solution pH 2.0.4000200.Dissolve 6.57g of potassium chloride R in water R and add 119.0mL of 0.1M hydrochloric acid .Dilute to 1000.0mL with water R .Phosphate buffer solution pH 2.0.4007900.Dissolve 8.95g of disodium hydrogen phosphate R and 3.40g of potassium dihydrogen phosphate R in water R and dilute to 1000.0mL with the same solvent.If necessary adjust the pH with phosphoric acid R .Sulfate buffer solution pH 2.0.4008900.Dissolve 132.1g of ammonium sulfate R in water R and dilute to 500.0mL with the same solvent (Solution A).Carefully and with constant cooling stir 14mL of sulfuric acid R into about 400mL of water R ;allow to cool and dilute to 500.0mL with water R (Solution B).Mix equal volumes of solutions A and B.Adjust the pH if necessary.Buffer solution pH 2.2.4010500.Mix 6.7mL of phosphoric acid R with 55.0mL of a 40g/Lsolution of sodium hydroxide R and dilute to 1000.0mL with water R .Buffer solution pH 2.5.4000300.Dissolve 100g of potassium dihydrogen phosphate R in 800mL of water R ;adjust to pH 2.5with hydrochloric acid R anddilute to 1000.0mL with water R .Buffer solution pH 2.5R1.4000400.To 4.9g of dilute phosphoric acid R add 250mL of water R .Adjust the pH with dilute sodium hydroxide solution R anddilute to 500.0mL with water R .0.2M Phosphate buffer solution pH 2.5.4014100.Dissolve 27.2g of potassium dihydrogen phosphate R in about900mL of water R ,adjust to pH 2.5with phosphoric acid Rand dilute to 1.0L with water R .Phosphate buffer solution pH 2.8.4010600.Dissolve 7.8g of sodium dihydrogen phosphate R in 900mL ofwater R ,adjust to pH 2.8with phosphoric acid R and dilute to1000mL with the same solvent.Buffer solution pH 3.0.4008000.Dissolve 21.0g of citric acid R in 200mL of 1M sodiumhydroxide and dilute to 1000mL with water R .Dilute 40.3mL of this solution to 100.0mL with 0.1M hydrochloric acid .0.25M Citrate buffer solution pH 3.0.4012600.Dissolve 5.3g of citric acid R in 80mL of water R .Adjust thepH with 1M sodium hydroxide and dilute to 100.0mL with water R .0.1M Phosphate buffer solution pH 3.0.4011500.Dissolve 12.0g of anhydrous sodium dihydrogen phosphate R in water R ,adjust the pH with dilute phosphoric acid R1and dilute to 1000mL with water R .Phosphate buffer solution pH 3.0.4000500.Mix 0.7mL of phosphoric acid R with 100mL of water R .Dilute to 900mL with the same solvent.Adjust to pH 3.0with strong sodium hydroxide solution R and dilute to 1000mL with water R .Phosphate buffer solution pH 3.0R1.4010000.Dissolve 3.40g of potassium dihydrogen phosphate R in900mL of water R .Adjust to pH 3.0with phosphoric acid R and dilute to 1000.0mL with water R .Phosphate buffer solution pH 3.2.4008100.To 900mL of a 4g/L solution of sodium dihydrogenphosphate R ,add 100mL of a 2.5g/L solution of phosphoric acid R .Adjust the pH if necessary.Phosphate buffer solution pH 3.2R1.4008500.Adjust a 35.8g/L solution of disodium hydrogen phosphate R to pH 3.2with dilute phosphoric acid R .Dilute 100.0mL of the solution to 2000.0mL with water R .EUROPEAN PHARMACOPOEIA 8.0 4.1.3.BuffersolutionsBuffer solution pH 3.5.4000600.Dissolve 25.0g of ammonium acetate R in 25mL of water R and add 38.0mL of hydrochloric acid R1.Adjust the pH if necessary with dilute hydrochloric acid R or dilute ammonia R1.Dilute to 100.0mL with water R .Phosphate buffer solution pH 3.5.4000700.Dissolve 68.0g of potassium dihydrogen phosphate R in water R and dilute to 1000.0mL with the same solvent.Adjustthe pH with phosphoric acid R .Buffer solution pH 3.6.4000800.To 250.0mL of 0.2M potassium hydrogen phthalate R add11.94mL of 0.2M hydrochloric acid .Dilute to 1000.0mLwith water R .Buffer solution pH 3.7.4000900.To 15.0mL of acetic acid R add 60mL of ethanol (96percent)R and 20mL of water R .Adjust to pH 3.7by the addition of ammonia R .Dilute to 100.0mL with water R .Buffered copper sulfate solution pH 4.0.4001000.Dissolve 0.25g of copper sulfate R and 4.5g of ammonium acetate R in dilute acetic acid R and dilute to 100.0mL with the same solvent.0.1M Sodium acetate buffer solution pH 4.0.4013800.Dissolve 822mg of sodium acetate R in 100mL of water R (solution A).Dilute 1.44mL of glacial acetic acid R in 250mL of water R (solution B).Titrate 100mL of solution B using about 20mL of solution A.Acetate buffer solution pH 4.4.4001100.Dissolve 136g of sodium acetate R and 77g of ammonium acetate R in water R and dilute to 1000.0mL with the same solvent;add 250.0mL of glacial acetic acid R and mix.Phthalate buffer solution pH 4.4.4001200.Dissolve 2.042g of potassium hydrogen phthalate R in 50mL of water R ,add 7.5mL of 0.2M sodium hydroxide and dilute to 200.0mL with water R .Acetate buffer solution pH 4.5.4012500.Dissolve 77.1g of ammonium acetate R in water R .Add 70mL of glacial acetic acid R and dilute to 1000.0mL with water R .0.5M Ammonium acetate buffer solution pH 4.5.4014200.Mix 14.3mL of glacial acetic acid R and 470mL of water Rand adjust to pH 4.5with concentrated ammonia R .Dilute to 500.0mL with water R .0.05M Phosphate buffer solution pH 4.5.4009000.Dissolve 6.80g of potassium dihydrogen phosphate R in1000.0mL of water R .The pH of the solution is 4.5.Sodium acetate buffer solution pH 4.5.4010100.Dissolve 63g of anhydrous sodium acetate R in water R ,add 90mL acetic acid R and adjust to pH 4.5,and dilute to1000mL with water R .Acetate buffer solution pH 4.6.4001400.Dissolve 5.4g of sodium acetate R in 50mL of water R ,add2.4g of glacial acetic acid R and dilute to 100.0mL withwater R .Adjust the pH if necessary.Succinate buffer solution pH 4.6.4001500.Disssolve 11.8g of succinic acid R in a mixture of 600mL ofwater R and 82mL of 1M sodium hydroxide and dilute to1000.0mL with water R .Acetate buffer solution pH 4.7.4001600.Dissolve 136.1g of sodium acetate R in 500mL of water R .Mix 250mL of this solution with 250mL of dilute acetic acid R .Shake twice with a freshly prepared,filtered,0.1g/L solution of dithizone R in chloroform R .Shake with carbon tetrachloride R until the extract is colourless.Filter the aqueous layer to remove traces of carbon tetrachloride.Acetate buffer solution pH 4.7R1.4013600.Dissolve 136.1g of sodium acetate R in 500mL of water R .Mix 250mL of this solution with 250mL of dilute acetic acid R .Acetate buffer solution pH 5.0.4009100.To 120mL of a 6g/L solution of glacial acetic acid R add 100mL of 0.1M potassium hydroxide and about 250mL ofwater R .Mix.Adjust the pH to 5.0with a 6g/L solution ofacetic acid R or with 0.1M potassium hydroxide and dilute to 1000.0mL with water R .Citrate buffer solution pH 5.0.4010700.Prepare a solution containing 20.1g/L of citric acid R and 8.0g/L of sodium hydroxide R .Adjust the pH with dilute hydrochloric acid R .0.2M Deuterated sodium phosphate buffer solution pH 5.0.4013900.Dissolve 2.76g of sodium dihydrogen phosphate monohydrate R in 90mL of deuterium oxide R ,adjust the pH with a deuterated solution of phosphoric acid R or a deuterated 1M solution of sodium hydroxide R ,dilute to 100mL with deuterium oxide R and mix.Phosphate buffer solution pH 5.0.4011300.Dissolve 2.72g of potassium dihydrogen phosphate R in 800mL of water R .Adjust the pH with 1M potassium hydroxide and dilute to 1000mL with water R .Buffer solution pH 5.2.4001700.Dissolve 1.02g of potassium hydrogen phthalate R in 30.0mL of 0.1M sodium hydroxide .Dilute to 100.0mL with water R .0.067M Phosphate buffer solution pH 5.4.4012000.Mix appropriate volumes of a 23.99g/L solution of disodium hydrogen phosphate R with a 9.12g/L solution of sodium dihydrogen phosphate monohydrate R to obtain pH 5.4.Acetate-edetate buffer solution pH 5.5.4001900.Dissolve 250g of ammonium acetate R and 15g sodiumedetate R in 400mL of water R and add 125mL of glacial acetic acid R .Buffer solution pH 5.5.4001800.Dissolve 54.4g of sodium acetate R in 50mL of water R ,heating to 35°C if necessary.After cooling,slowly add 10mL of anhydrous acetic acid R .Shake and dilute to 100.0mL withwater R .Phosphate buffer solution pH 5.5.4002000.Dissolve 13.61g of potassium dihydrogen phosphate R inwater R and dilute to 1000.0mL with the same solvent(solution A).Dissolve 35.81g of disodium hydrogen phosphate R in water R and dilute to 1000.0mL with the same solvent (solution B).Mix 96.4mL of solution A and 3.6mL of solution B.Phosphate-citrate buffer solution pH 5.5.4008700.Mix 56.85mL of a 28.4g/L solution of anhydrous disodium hydrogen phosphate R and 43.15mL of a 21g/L solution of citric acid R .Phosphate buffer solution pH 5.6.4011200.Dissolve 0.908g of potassium dihydrogen phosphate R in water R and dilute to 100.0mL with the same solvent (solution A).Dissolve 1.161g of dipotassium hydrogenphosphate R in water R and dilute to 100.0mL with the same solvent (solution B).Mix 94.4mL of solution A and 5.6mL of solution B.If necessary,adjust to pH 5.6using solution A or solution B.4.1.3.Buffer solutions EUROPEAN PHARMACOPOEIA8.0Phosphate buffer solution pH5.8.4002100.Dissolve1.19g of disodium hydrogen phosphate dihydrate R and8.25g of potassium dihydrogen phosphate R in water R and dilute to1000.0mL with the same solvent.Acetate buffer solution pH6.0.4002200.Dissolve100g of ammonium acetate R in300mL of water R, add4.1mL of glacial acetic acid R,adjust the pH if necessary using ammonia R or acetic acid R and dilute to500.0mL with water R.Diethylammonium phosphate buffer solution pH6.0. 4002300.Dilute68mL of phosphoric acid R to500mL with water R. To25mL of this solution add450mL of water R and6mLof diethylamine R,adjust to pH6±0.05,if necessary,using diethylamine R or phosphoric acid R and dilute to500.0mL with water R.Phosphate buffer solution pH6.0.4002400.Mix63.2mL of a71.5g/L solution of disodium hydrogen phosphate R and36.8mL of a21g/L solution of citric acid R. Phosphate buffer solution pH6.0R1.4002500.Dissolve6.8g of sodium dihydrogen phosphate R in water R and dilute to1000.0mL with water R.Adjust the pH with strong sodium hydroxide solution R.Phosphate buffer solution pH6.0R2.4002600.To250.0mL of0.2M potassium dihydrogen phosphate R add 28.5mL of0.2M sodium hydroxide and dilute to1000.0mL with water R.Phosphate buffer solution pH6.4.4002800.Dissolve2.5g of disodium hydrogen phosphate R,2.5g of sodium dihydrogen phosphate R and8.2g of sodium chloride R in950mL of water R.Adjust the pH of the solution to6.4with 1M sodium hydroxide or1M hydrochloric acid,if necessary. Dilute to1000.0mL with water R.0.5M Phthalate buffer solution pH6.4.4009200. Dissolve100g of potassium hydrogen phthalate R in water R and dilute to1000.0mL with the same solvent.Adjust the pH if necessary,using strong sodium hydroxide solution R. Buffer solution pH6.5.4002900.Dissolve60.5g of disodium hydrogen phosphate R and46g of potassium dihydrogen phosphate R in water R.Add100mL of 0.02M sodium edetate and20mg of mercuric chloride R and dilute to1000.0mL with water R.Imidazole buffer solution pH6.5.4003000.Dissolve6.81g of imidazole R,1.23g of magnesium sulfate R and0.73g of calcium sulfate R in752mL of0.1M hydrochloric acid.Adjust the pH if necessary and dilute to1000.0mL with water R.0.1M phosphate buffer solution pH6.5.4010800. Dissolve13.80g of sodium dihydrogen phosphate monohydrate R in900mL of distilled water R.Adjust the pH using a400g/L solution of sodium hydroxide R.Dilute to 1000mL with distilled water R.Phosphate buffer solution pH6.5.4012800.Dissolve2.75g of sodium dihydrogen phosphate R and4.5g of sodium chloride R in500mL of water R.Adjust the pH with phosphate buffer solution pH8.5R.Buffer solution pH6.6.4003100.To250.0mL of0.2M potassium dihydrogen phosphate R add 89.0mL of0.2M sodium hydroxide.Dilute to1000.0mL with water R.0.1M Phosphate buffer solution pH6.7.4014300. Dissolve15.6g of sodium dihydrogen phosphate R in water R and dilute to1.0L with the same solvent.Dissolve17.8g of disodium hydrogen phosphate dihydrate R in water R and dilute to1.0L with the same solvent.Mix the solutions,check the pH and if necessary adjust to pH6.7.Phosphate buffered saline pH6.8.4003200.Dissolve1.0g of potassium dihydrogen phosphate R,2.0gof dipotassium hydrogen phosphate R and8.5g of sodium chloride R in900mL of water R,adjust the pH if necessary and dilute to1000.0mL with the same solvent. Phosphate buffer solution pH6.8.4003300.Mix77.3mL of a71.5g/L solution of disodium hydrogen phosphate R with22.7mL of a21g/L solution of citric acid R. Phosphate buffer solution pH6.8R1.4003400.To51.0mL of a27.2g/L solution of potassium dihydrogen phosphate R add49.0mL of a71.6g/L solution of disodium hydrogen phosphate R.Adjust the pH if necessary. Storage:at2°C to8°C.1M tris-hydrochloride buffer solution pH6.8.4009300. Dissolve60.6g of tris(hydroxymethyl)aminomethane R in 400mL of water R.Adjust the pH with hydrochloric acid R and dilute to500.0mL with water R.Buffer solution pH7.0.4003500.To1000mL of a solution containing18g/L of disodium hydrogen phosphate R and23g/L of sodium chloride R add sufficient(about280mL)of a solution containing7.8g/Lof sodium dihydrogen phosphate R and23g/L of sodium chloride R to adjust the pH.Dissolve in the solution sufficient sodium azide R to give a0.2g/L solution.Maleate buffer solution pH7.0.4003600.Dissolve10.0g of sodium chloride R,6.06g oftris(hydroxymethyl)aminomethane R and4.90g of maleic anhydride R in900mL of water R.Adjust the pH using a 170g/L solution of sodium hydroxide R.Dilute to1000.0mL with water R.Storage:at2°C to8°C;use within3days.0.025M Phosphate buffer solution pH7.0.4009400.Mix1volume of0.063M phosphate buffer solution pH7.0R with1.5volumes of water R.0.03M Phosphate buffer solution pH7.0.4010300. Dissolve5.2g of dipotassium hydrogen phosphate R in900mL of water for chromatography R.Adjust the solution to pH7.0±0.1using phosphoric acid R and dilute to1000mL with water for chromatography R.0.05M Phosphate buffer solution pH7.0.4012400.Mix34mL of water R and100mL of0.067M phosphate buffer solution pH7.0R.0.063M Phosphate buffer solution pH7.0.4009500. Dissolve5.18g of anhydrous disodium hydrogen phosphate R and3.65g of sodium dihydrogen phosphate monohydrate R in 950mL of water R and adjust the pH with phosphoric acid R; dilute to1000.0mL with water R.0.067M Phosphate buffer solution pH7.0.4003800. Dissolve0.908g of potassium dihydrogen phosphate Rin water R and dilute to100.0mL with the same solvent (solution A).Dissolve2.38g of disodium hydrogen phosphate R in water R and dilute to100.0mL with the same solvent (solution B).Mix38.9mL of solution A and61.1mL of solution B.Adjust the pH if necessary.EUROPEAN PHARMACOPOEIA 8.0 4.1.3.Buffersolutions0.1M Phosphate buffer solution pH 7.0.4008200.Dissolve 1.361g of potassium dihydrogen phosphate R in water R and dilute to 100.0mL with the same solvent.Adjust the pH using a 35g/L solution of disodium hydrogen phosphate R .Phosphate buffer solution pH 7.0.4003700.Mix 82.4mL of a 71.5g/L solution of disodium hydrogen phosphate R with 17.6mL of a 21g/L solution of citric acid R .Phosphate buffer solution pH 7.0R1.4003900.Mix 250.0mL of 0.2M potassium dihydrogen phosphate R and 148.2mL of a 8g/L solution of sodium hydroxide R ,adjust the pH if necessary.Dilute to 1000.0mL with water R .Phosphate buffer solution pH 7.0R2.4004000.Mix 50.0mL of a 136g/L solution of potassium dihydrogenphosphate R with 29.5mL of 1M sodium hydroxide and dilute to 100.0mL with water R .Adjust the pH to 7.0±0.1.Phosphate buffer solution pH 7.0R3.4008600.Dissolve 5g of potassium dihydrogen phosphate R and 11gof dipotassium hydrogen phosphate R in 900mL of water R .Adjust to pH 7.0with dilute phosphoric acid R or dilute sodium hydroxide solution R .Dilute to 1000mL with water R and mix.Phosphate buffer solution pH 7.0R4.4010200.Dissolve 28.4g of anhydrous disodium hydrogen phosphate R and 18.2g of potassium dihydrogen phosphate R in water R and dilute to 500mL with the same solvent.Phosphate buffer solution pH 7.0R5.4011400.Dissolve 28.4g of anhydrous disodium hydrogen phosphate R in 800mL of water R .Adjust the pH using a 30per cent m/m solution of phosphoric acid R and dilute to 1000mL with water R .Tetrabutylammonium buffer solution pH 7.0.4010900.Dissolve 6.16g of ammonium acetate R in a mixture of 15mL of tetrabutylammonium hydroxide solution (400g/L)R and 185mL of water R .Adjust the pH with nitric acid R .Buffered salt solution pH 7.2.4004300.Dissolve in water R 8.0g of sodium chloride R ,0.2g of potassium chloride R ,0.1g of anhydrous calcium chloride R ,0.1g of magnesium chloride R ,3.18g of disodium hydrogen phosphate R and 0.2g of potassium dihydrogen phosphate R and dilute to 1000.0mL with water R .Buffer solution pH 7.2.4004100.To 250.0mL of 0.2M potassium dihydrogen phosphate R add 175.0mL of 0.2M sodium hydroxide .Dilute to 1000.0mL with water R .Adjust the pH if necessary.Phosphate-albumin buffered saline pH 7.2.4004400.Dissolve 10.75g of disodium hydrogen phosphate R ,7.6g of sodium chloride R and 10g of bovine albumin R in water R and dilute to 1000.0mL with the same solvent.Immediately before use adjust the pH using dilute sodium hydroxide solution R or dilute phosphoric acid R .Phosphate-albumin buffered saline pH 7.2R1.4009600.Dissolve 10.75g of disodium hydrogen phosphate R ,7.6g of sodium chloride R and 1g of bovine albumin R in water R and dilute to 1000.0mL with the same solvent.Immediately before use adjust the pH using dilute sodium hydroxide solution Ror dilute phosphoric acid R .Phosphate buffer solution pH 7.2.4004200.Mix 87.0mL of a 71.5g/L solution of disodium hydrogenphosphate R with 13.0mL of a 21g/L solution of citric acid R .Imidazole buffer solution pH 7.3.4004500.Dissolve 3.4g of imidazole R and 5.8g of sodium chloride R in water R ,add 18.6mL of 1M hydrochloric acid and dilute to 1000.0mL with water R .Adjust the pH if necessary.Barbital buffer solution pH 7.4.4004700.Mix 50mL of a solution in water R containing 19.44g/L of sodium acetate R and 29.46g/L of barbital sodium R with 50.5mL of 0.1M hydrochloric acid ,add 20mL of an 85g/L of sodium chloride R and dilute to 250mL with water R .Buffer solution pH 7.4.4004600.Dissolve 0.6g of potassium dihydrogen phosphate R ,6.4g of disodium hydrogen phosphate R and 5.85g of sodium chloride R in water R ,and dilute to 1000.0mL with the same solvent.Adjust the pH if necessary.Phosphate buffered saline pH 7.4.4005000.Dissolve 2.38g of disodium hydrogen phosphate R ,0.19g of potassium dihydrogen phosphate R and 8.0g of sodiumchloride R in water.Dilute to 1000.0mL with the same solvent.Adjust the pH if necessary.Phosphate buffer solution pH 7.4.4004800.Add 250.0mL of 0.2M potassium dihydrogen phosphate R to 393.4mL of 0.1M sodium hydroxide .Tris(hydroxymethyl)aminomethane buffer solution pH 7.4.4012100.Dissolve 30.3g of tris(hydroxymethyl)aminomethane R in approximately 200mL of water R .Add 183mL of 1M hydrochloric acid .Dilute to 500.0mL with water R .Note:the pH is 7.7-7.8at room temperature and 7.4at 37°C.This solution is stable for several months at 4°C.Tris(hydroxymethyl)aminomethane sodium chloride buffer solution pH 7.4.4004900.Dissolve 6.08g of tris(hydroxymethyl)aminomethane R ,8.77g of sodium chloride R in 500mL of distilled water R .Add 10.0g of bovine albumin R .Adjust the pH using hydrochloric acid R .Dilute to 1000.0mL with distilled water R .Tris(hydroxymethyl)aminomethane sodium chloride buffer solution pH 7.4R1.4012200.Dissolve 0.1g of bovine albumin R in a mixture containing 2mL of tris(hydroxymethyl)aminomethane buffer solution pH 7.4R and 50mL of a 5.84mg/mL solution of sodium chloride R .Dilute to 100.0mL with water R .Tris-sodium acetate buffer solution pH 7.4.4012900.Dissolve 6.3g of tris(hydroxymethyl)aminomethane R and 4.9g of anhydrous sodium acetate R in 900mL of water R .Adjust to pH 7.4with sulfuric acid R and dilute to 1000mL with water R .Tris-sodium acetate-sodium chloride buffer solution pH 7.4.4013000.Dissolve 30.0g of tris(hydroxymethyl)aminomethane R ,14.5gof anhydrous sodium acetate R and 14.6g of sodium chloride R in 900mL of water R .Add 0.50g of bovine albumin R .Adjust to pH 7.4with sulfuric acid R and dilute to 1000mL with water R .Borate buffer solution pH 7.5.4005200.Dissolve 2.5g of sodium chloride R ,2.85g of disodium tetraborate R and 10.5g of boric acid R in water R and dilute to 1000.0mL with the same solvent.Adjust the pH if necessary.Storage :at 2°C to 8°C.Buffer (HEPES)solution pH 7.5.4009700.Dissolve 2.38g of 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid R in about 90mL of water R .Adjust thepH to 7.5with sodium hydroxide solution R .Dilute to 100mL with water R .4.1.3.Buffer solutions EUROPEAN PHARMACOPOEIA8.00.05M Phosphate buffer solution pH7.5.4014400. Dissolve0.89g of disodium hydrogen phosphate dihydrate R in about80mL of water R.Adjust to pH7.5with an8.5per cent V/V solution of phosphoric acid R and dilute to100.0mL with water R.0.2M Phosphate buffer solution pH7.5.4005400. Dissolve27.22g of potassium dihydrogen phosphate R in930mL of water R,adjust to pH7.5with a300g/L solution of potassium hydroxide R and dilute to1000.0mL with water R.0.33M Phosphate buffer solution pH7.5.4005300. Dissolve119.31g of disodium hydrogen phosphate R in water R and dilute to1000.0mL with the same solvent(solution A). Dissolve45.36g of potassium dihydrogen phosphate R in water R and dilute to1000.0mL with the same solvent (solution B).Mix85mL of solution A and15mL of solution B. Adjust the pH if necessary.0.05M Tris-hydrochloride buffer solution pH7.5.4005600. Dissolve6.057g of tris(hydroxymethyl)aminomethane R in water R and adjust the pH with hydrochloric acid R.Dilute to 1000.0mL with water R.1M Tris-hydrochloride buffer solution pH7.5.4014500. Dissolve12.11g of tris(hydroxymethyl)aminomethane R in 90mL of water R,adjust to pH7.5with hydrochloric acid R and dilute to100.0mL with water R.Tris(hydroxymethyl)aminomethane buffer solution pH7.5. 4005500.Dissolve7.27g of tris(hydroxymethyl)aminomethane R and 5.27g of sodium chloride R in water R,and adjust the pH if necessary.Dilute to1000.0mL with water R.Sodium citrate buffer solution pH7.8(0.034M sodium citrate,0.101M sodium chloride).4009800.Dissolve10.0g of sodium citrate R and5.90g of sodium chloride R in900mL of water R.Adjust the pH by addition of hydrochloric acid R and dilute to1000mL with water R.0.0015M Borate buffer solution pH8.0.4006000. Dissolve0.572g of disodium tetraborate R and2.94g of calcium chloride R in800mL of water R.Adjust the pH with 1M hydrochloric acid.Dilute to1000.0mL with water R. Buffer solution pH8.0.4005900.To50.0mL of0.2M potassium dihydrogen phosphate R add 46.8mL of0.2M sodium hydroxide.Dilute to200.0mL with water R.Buffer solution pH8.0R1.4010400.Dissolve20g of dipotassium hydrogen phosphate R in900mL of water R.Adjust the pH with phosphoric acid R.Dilute to 1000mL with water R.0.02M Phosphate buffer solution pH8.0.4006100.To50.0mL of0.2M potassium dihydrogen phosphate R add 46.8mL of0.2M sodium hydroxide.Dilute to500.0mL with water R.0.02M Sodium phosphate buffer solution pH8.0.4013700. Dissolve0.31g of sodium dihydrogen phosphate R in70mL of water R and adjust to pH8.0with1M sodium hydroxide,then dilute to100mL with water R.0.1M Phosphate buffer solution pH8.0.4008400. Dissolve0.523g of potassium dihydrogen phosphate R and 16.73g of dipotassium hydrogen phosphate R in water R and dilute to1000.0mL with the same solvent.1M Phosphate buffer solution pH8.0.4007800.Dissolve136.1g of potassium dihydrogen phosphate R in water R,adjust the pH with1M sodium hydroxide.Dilute to 1000.0mL with water R.1M Tris-hydrochloride buffer solution pH8.0.4012700. Dissolve121.1g of tris(hydroxymethyl)aminomethane R and 1.47g of calcium chloride R in900mL of water R.Adjust the pH with hydrochloric acid R and dilute to1000.0mL with water R.Tris-hydrochloride buffer solution pH8.0.4012300. Dissolve1.21g of tris(hydroxymethyl)aminomethane R and 29.4mg of calcium chloride R in water R.Adjust the pH with 1M hydrochloric acid and dilute to100.0mL with water R. Tris-sodium acetate buffer solution pH8.0.4013100. Dissolve6.3g of tris(hydroxymethyl)aminomethane R and 4.9g of anhydrous sodium acetate R in900mL of water R. Adjust to pH8.0with sulfuric acid R and dilute to1000mL with water R.Tris-sodium acetate-sodium chloride buffer solutionpH8.0.4013200.Dissolve30.0g of tris(hydroxymethyl)aminomethane R,14.5g of anhydrous sodium acetate R and14.6g of sodium chloride R in900mL of water R.Add0.50g of bovine albumin R.Adjust to pH8.0with sulfuric acid R and dilute to1000mL with water R.Tris(hydroxymethyl)aminomethane buffer solution pH8.1. 4006200.Dissolve0.294g of calcium chloride R in40mL oftris(hydroxymethyl)aminomethane solution R and adjust the pH with1M hydrochloric acid.Dilute to100.0mL with water R.Tris-glycine buffer solution pH8.3.4006300.Dissolve6.0g of tris(hydroxymethyl)aminomethane R and 28.8g of glycine R in water R and dilute to1000.0mL with the same solvent.Dilute1volume to10volumes with water R immediately before use.Tris-hydrochloride buffer solution pH8.3.4011800. Dissolve9.0g of tris(hydroxymethyl)aminomethane R in2.9L of water R.Adjust the pH with1M hydrochloric acid.Adjust the volume to3L with water R.0.05M Tris-hydrochloride buffer solution pH9.0.4013500. Dissolve0.605g of tris(hydroxymethyl)aminomethane R in water R.Adjust the pH with1M hydrochloric acid and dilute to100.0mL with water R.Barbital buffer solution pH8.4.4006400.Dissolve8.25g of barbital sodium R in water R and dilute to 1000.0mL with the same solvent.Tris-EDTA BSA buffer solution pH8.4.4006500. Dissolve6.1g of tris(hydroxymethyl)aminomethane R,2.8g of sodium edetate R,10.2g of sodium chloride R and10gof bovine albumin R in water R,adjust to pH8.4using1M hydrochloric acid and dilute to1000.0mL with water R.Tris(hydroxymethyl)aminomethane-EDTA buffer solution pH8.4.4006600.Dissolve5.12g of sodium chloride R,3.03g oftris(hydroxymethyl)aminomethane R and1.40g of sodium edetate R in250mL of distilled water R.Adjust the pH to8.4 using hydrochloric acid R.Dilute to500.0mL with distilled water R.Guanidine-tris(hydroxymethyl)aminomethane-EDTA buffer solution pH8.5.4014600.Dissolve1.0g of sodium edetate R,12.1g oftris(hydroxymethyl)aminomethane R and57.0g of guanidine hydrochloride R in35mL of water R.Adjust topH8.5with hydrochloric acid R and dilute to100mL with water R.。