USP 35阿司匹林原料药质量标准.pdf

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1、USP 35Official Monographs/Aspirin 2245W=weight of Sample(mg)USP REFERENCE STANDARDS 11Acceptance criteria:98.5%101.5%on the dried basisUSP Aspartic Acid RSIMPURITIES RESIDUE ON IGNITION 281:NMT 0.1%.CHLORIDE AND SULFATE,Chloride 221Sample solution:Dissolve 0.7 g of Aspartic Acid in 10 mLAspirinof di

2、luted nitric acid,and dilute with water to 15 mL.Acceptance criteria:The Sample solution shows no morechloride than corresponds to 0.20 mL of 0.020 Nhydrochloric acid(NMT 0.02%).CHLORIDE AND SULFATE,Sulfate 221Sample solution:Dissolve 0.8 g of Aspartic Acid in 4 mL ofhydrochloric acid,and dilute wit

3、h water to 15 mL.C9H8O4180.16Acceptance criteria:The Sample solution shows no moreBenzoic acid,2-(acetyloxy)-.sulfate than corresponds to 0.25 mL of 0.020 N sulfuric acidSalicylic acid acetate 50-78-2.(NMT 0.03%).IRON 241:NMT 10 ppm Aspirin contains not less than 99.5 per cent and HEAVY METALS,Metho

4、d II 231:NMT 10 ppmnot more than 100.5 per cent of C9H8O4,calcu-CHROMATOGRAPHIC PURITYSystem suitability solution:10 mg each of USP Asparticlated on the dried basis.Acid RS and glutamic acid in 2 mL of ammonia TS.DilutePackaging and storagePreserve in tight containers.with water to 25.0 mL.Standard

5、solution:Transfer 5 mg of USP Aspartic Acid RS toUSP Reference standards 11a 100-mL volumetric flask,dissolve in 2 mL of 17%USP Aspirin RSammonia solution(prepared by diluting ammoniumIdentificationhydroxide,6 in 10),and dilute with water to volume.Sample solution:Transfer 0.1 g of Aspartic Acid to

6、a 10-mLA:Heat it with water for several minutes,cool,and add 1 orvolumetric flask,dissolve in 2 mL of 17%ammonia solution2 drops of ferric chloride TS:a violet-red color is produced.(prepared by diluting ammonium hydroxide,6 in 10),andB:Infrared Absorption 197K.dilute with water to volume.Loss on dr

7、ying 731Dry it over silica gel for 5 hours:itChromatographic systemloses not more than 0.5%of its weight.(See Chromatography 621,Thin-Layer Chromatography.)Readily carbonizable substances 271Dissolve 500 mg inMode:TLC5 mL of sulfuric acid:the solution has no more color thanAdsorbent:0.25-mm layer of

8、 chromatographic silica gelMatching Fluid Q.mixtureApplication volume:5 LResidue on ignition 281:not more than 0.05%.Developing solvent system:Butyl alcohol,glacial aceticSubstances insoluble in sodium carbonate TSA solutionacid,and water(3:1:1)of 500 mg in 10 mL of warm sodium carbonate TS is clear

9、.Spray reagent:2 mg/mL of ninhydrin in a mixture of butylChloride 221Boil 1.5 g with 75 mL of water for 5 minutes,alcohol and 2 N acetic acid(95:5)cool,add sufficient water to restore the original volume,andSystem suitabilityfilter.A 25-mL portion of the filtrate shows no more chlorideSample:System

10、suitability solutionthan corresponds to 0.10 mL of 0.020 N hydrochloric acidSuitability requirement:The chromatogram of the System(0.014%).suitability solution exhibits two clearly separated spots.Sulfate Dissolve 6.0 g in 37 mL of acetone,and add 3 mL ofAnalysiswater.Titrate potentiometrically with

11、 0.02 M lead per chlorate,Samples:System suitability solution,Standard solution,andprepared by dissolving 9.20 g of lead per chlorate in water toSample solutionmake 1000 mL of solution,using a pH meter capable of a mini-Proceed as directed in the chapter,except dr y the plate atmum reproducibility o

12、f 0.1 mV(see pH 791)and equipped80 for 30 min,spray with Spray reagent,and heat at 80 with an electrode system consisting of a lead-specific electrodefor 30 min.Examine the plate under white light.and a silversilver chloride reference glass-sleeved electrodeAcceptance criteria:No secondary spot from

13、 the Samplecontaining a solution of tetraethylammonium per chlorate in gla-solution is larger or more intense than the principal spotcial acetic acid(1 in 44)(see Titrimetry 541):not more thanfrom the Standard solution.1.25 mL of 0.02 M lead per chlorate is consumed(0.04%).Individual impurities:NMT

14、0.5%NOTEAfter use,rinse the lead-specific electrode with water,Total impurities:NMT 2.0%drain the reference electrode,flush with water,rinse with meth-anol,and allow to dr y.SPECIFIC TESTS OPTICAL ROTATION,Specific Rotation 781SHeavy metalsDissolve 2 g in 25 mL of acetone,and add 1Sample solution:80

15、 mg/mL in 6 N hydrochloric acidmL of water.Add 1.2 mL of thioacetamideglycerin base TSAcceptance criteria:+24.0 to+26.0,at 20and 2 mL of pH 3.5 Acetate Buffer(see Heavy Metals 231),and LOSS ON DRYING 731:Dry a sample at 105 for 3 h:it losesallow to stand for 5 minutes:any color produced is not darke

16、rNMT 0.5%of its weight.than that of a control made with 25 mL of acetone and 2 mLof Standard Lead Solution(see Heavy Metals 231),treated inADDITIONAL REQUIREMENTSthe same manner.The limit is 10 g per g.PACKAGING AND STORAGE:Preserve in well-closed containers,Limit of free salicylic acidDissolve 2.5

17、g in sufficient alco-and store protected from light.hol to make 25.0 mL.T o each of two matched color-compari-son tubes add 48 mL of water and 1 mL of a freshly prepared,diluted ferric ammonium sulfate solution(prepared by adding 1mL of 1 N hydrochloric acid to 2 mL of ferric ammonium sul-fate TS an

18、d diluting with water to 100 mL).Into one tube pipet1 mL of a standard solution of salicylic acid in water,containing0.10 mg of salicylic acid per mL.Into the second tube pipet 1mL of the 1 in 10 solution of Aspirin.Mix the contents of eachtube:after 30 seconds,the color in the second tube is notOff

19、icial from May 1,2012Copyright(c)2011 The United States Pharmacopeial Convention.All rights reserved.Accessed from 128.83.63.20 by nEwp0rt1 on Mon Nov 21 22:19:00 EST 20112246 Aspirin/Official MonographsUSP 35more intense than that in the tube containing the salicylic acidStandard preparationPrepare

20、 a solution in Diluting solution(0.1%).having known concentrations of about 0.4 mg of USP AspirinRS and 0.01 mg of USP Salicylic Acid RS per mL.AssayPlace about 1.5 g of Aspirin,accurately weighed,in aflask,add 50.0 mL of 0.5 N sodium hydroxide VS,and boil theAssay preparationWeigh and finely powder

21、 not fewer thanmixture gently for 10 minutes.Add phenolphthalein TS,and10 Boluses.Transfer an accurately weighed portion of the pow-titrate the excess sodium hydroxide with 0.5 N sulfuric acid VS.der,equivalent to about 400 mg of aspirin,to a 100-mL volu-Perform a blank determination(see Residual Ti

22、trations under Ti-metric flask,dilute with Diluting solution to volume,and stir bytrimetry 541).Each mL of 0.5 N sodium hydroxide is equiva-mechanical means for about 15 minutes.Pass a portion of thislent to 45.04 mg of C9H8O4.solution through a filter having a 0.5-m or finer porosity,anduse the fil

23、trate as the Assay preparation.Chromatographic system(see Chromatography 621)Theliquid chromatograph is equipped with a 254-nm detector and.a 4.6-mm 25-cm column that contains 5-m packing L1.TheAspirin Bolusesflow rate is about 1 mL per minute.Chromatograph the Stan-dard preparation,and record the p

24、eak responses as directed for Aspirin Boluses contain not less than 90.0 per-Procedure:the relative retention times are about 0.6 for salicylicacid and 1.0 for aspirin,and the relative standard deviation ofcent and not more than 110.0 per cent of thethe aspirin peak response for replicate injections

25、 is not morelabeled amount of aspirin(C9H8O4).than 2.0%.Packaging and storagePreserve in tight containers.ProcedureSeparately inject equal volumes(about 20 L)ofthe Standard preparation and the Assay preparation into theLabelingLabel Boluses to indicate that they are for veterinar ychromatograph,reco

26、rd the chromatograms,and measure theuse only.responses for the major peaks.Calculate the quantity,in mg,ofUSP Reference standards 11aspirin(C9H8O4)in the portion of Boluses taken by the formula:USP Aspirin RS1000C(rU/rS)USP Salicylic Acid RSIdentificationin which C is the concentration,in mg per mL,

27、of USP AspirinA:Crush 1 Bolus,boil a portion of the powder,equivalent toRS in the Standard preparation;and rU and rS are the aspirinabout 300 mg of aspirin,with 50 mL of water,cool,and add apeak responses obtained from the Assay preparation and thedrop of ferric chloride TS:a violet-red color is pro

28、duced.Standard preparation,respectively.B:The retention time of the aspirin peak in the chromato-gram of the Assay preparation corresponds to that in the chro-matogram of the Standard preparation,as obtained in the Assay.Dissolution 711Aspirin CapsulesMedium:0.5 M phosphate buffer,pH 7.4;900 mL.Appa

29、ratus 2:75 rpm.Aspirin Capsules contain not less than 93.0 per-Time:45 minutes.cent and not more than 107.0 per cent of theDiluting solutionPrepare a mixture of acetonitrile and for-labeled amount of aspirin(C9H8O4).mic acid(99:1).NOTECapsules that are enteric-coated or theProcedureDetermine the amo

30、unt of aspirin(C9H8O4)dis-contents of which are enteric-coated meet thesolved by employing UV absorption at the wavelength of theisosbestic point of aspirin and salicylic acid at 265 2 nm onrequirements for Aspirin Delayed-Release Capsules.filtered portions of the solution under test,suitably dilute

31、d withPackaging and storagePreserve in tight containers.Diluting solution,if necessary,in comparison with a Standardsolution having a known concentration of USP Aspirin RS in theUSP Reference standards 11same Medium.NOTEPrepare the Standard solution at the timeUSP Aspirin RSof use.IdentificationTole

32、rancesNot less than 80%(Q)of the labeled amount ofC9H8O4 is dissolved in 45 minutes.A:Heat about 100 mg of the Capsule contents with 10 mLof water for several minutes,cool,and add 1 drop of ferricUniformity of dosage units 905:meet the requirements.chloride TS:a violet-red color is produced.Limit of

33、 salicylic acidUsing the chromatograms of theB:Shake a quantity of the contents of Capsules,equivalentStandard preparation and the Assay preparation,obtained as di-to about 500 mg of aspirin,with 10 mL of alcohol for severalrected in the Assay,calculate the percentage of salicylic acidminutes.Centri

34、fuge the mixture.Pour off the clear supernatant(C7H6O3)in the portion of Boluses taken by the formula:and evaporate it to dr yness.Dry the residue in vacuum at 60 for 1 hour:the residue responds to Identification test B under100,000(C/WA)(rU/rS)Aspirin.in which C is the concentration,in mg per mL,of

35、 USP SalicylicDissolution 711Acid RS in the Standard preparation;WA is the quantity,in mg,Medium:0.05 M acetate buffer,prepared by mixing 2.99of aspirin(C9H8O4)in the portion of Boluses taken,as deter-g of sodium acetate trihydrate and 1.66 mL of glacial aceticmined in the Assay;and rU and rS are th

36、e salicylic acid peakacid with water to obtain 1000 mL of solution having a pH ofresponses obtained from the Assay preparation and the Standard4.50 0.05;500 mL.preparation,respectively:not more than 0.3%is found.Apparatus 1:100 rpm.AssayTime:30 minutes.Mobile phaseDissolve 2 g of sodium 1-heptanesul

37、fonate inProcedureDetermine the amount of C9H8O4 dissolved froma mixture of 850 mL of water and 150 mL of acetonitrile,andUV absorbances at the wavelength of the isosbestic point ofadjust with glacial acetic acid to a pH of 3.4.Make any neces-aspirin and salicylic acid at 265 2 nm of filtered portio

38、ns ofsary adjustments(see System Suitability under Chromatographythe solution under test,suitably diluted with Medium,if neces-621).sary,in comparison with a Standard solution having a knownDiluting solutionPrepare a mixture of acetonitrile and for-concentration of USP Aspirin RS in the same Medium.NOTEmic acid(99:1).Official from May 1,2012Copyright(c)2011 The United States Pharmacopeial Convention.All rights reserved.Accessed from 128.83.63.20 by nEwp0rt1 on Mon Nov 21 22:19:00 EST 2011