容量滴定法的方法验证与认可

商军,王蓓,蔡金华,刘雅妮(,201103)[]2010-05-25[]A[]1002-1280(2010)09-0024-04[]O655.2[]以容量滴定法测定呋塞米原料药含量的验证过程为实例,具体阐述了容量滴定法的方法验证过程和验证结果的认可标准,以期为容量滴定法科学合理的验证与认可提供参考[]容量滴定法方法验证方法认可:(1970-),,,E-mai:[e-mail]ationandApprovaloftheVolumetricTitrationSHANGJun,WANGBe,iCAIJin-hua,LIUYa-ni(ShanghaiInstituteforVeterinaryDrug&FeedstuffsControl,Shanghai201103;China)Abstract:Theproceduresandapprovalcriteriaofapracticalexamplebyvolumetrictitrationfordeterminationoffurosemidewasdescribedinthisarticlesoastoprovidereferencesforscientificandreasonableverificationandapprovalofvolumetrictitration.Keywords:volumetrictitration;methodologicalverification;methodologicalapproval,,,,,,,,,[1-4],,,,,[2],(4)[5],4(/,,,)[6-10],,11.1仪器与试剂,25mL,A;,,ABC;,2005;,2005,0.1015moL/L;,;,1.2实验方法0.5g,,30mL,,,4242010,44(9):24~27/,1,(0.1moL/L),1mL(0.1moL/L)33.07mgC12H11ClN2O5S2[5],,,7,20%~90%,,0.5%miVi,,bobsaobs(sdv(V))2.1第一个判断标准成比例的系统误差(偏倚),,bobs()btheor0.3%;,0.5%(1)(2):()=(bobs-btheorbtheor)100(1)btheor=ZMrCr(2),bobs;btheor;Mr;Z;Cr2.2第二个判断标准额外的系统误差(偏倚),aobs0.4%,aobs0.6%()(),(3):()=(aobsVT)100(3)VT=btheormi(4),aobs;VT2.3第三个判断标准精密度(统计学误差),sdv(V)0.3%;,sdv(V)0.5%(5)(6)(7):()=(sdv(V)VT)100(5)sdv(V)=sddn-2(6)sdd=ni=1(Vi-aobs-bobsmi)2(7),sdv(V);Vi;mi;n2.4第四个判断标准偏相对偏差,,(10mL,8mL1mL),,(8):aobsVT+bobs-btheorbtheor100(8)2.5容量滴定方法限度确定,(6)11()1(%)(RSD)(x)/1.00.330.671.00.330.671.00.330.671.50.51.01.50.51.02.00.671.33:x=x-xtheorxtheor100,RSD(n6)1252010,44(9):24~27/,,,33.1成比例的系统误差(偏倚)的判断25mL20%40%50%70%80%90%,,7,1.2,,(Vi),(mi),,,22,29.669mL/g(A)29.677mL/g(B)29.653mL/g(C),2.1(1)(2)btheor=1330.750.1015=133.571=29.79mL/g,0.40%(A)0.37%(B)0.47%(C),2Ami(g)Vi(mL)Bmi(g)Vi(mL)Cmi(g)Vi(mL)0.16814.970.16744.980.16704.930.33609.930.33559.950.33579.980.420112.430.419312.460.420712.500.503314.880.504114.900.503715.010.587917.390.587117.400.587417.420.671719.950.671520.020.671919.980.755922.380.756022.400.755022.34:Vi=29.669mi-0.03138Vi=29.677mi-0.0008251Vi=29.653mi+0.016122,,0.5%33.2额外的系统误差(偏倚)的判断,-0.03138mL-0.0008251mL0.01612mL,2.2(3)(4)VT=29.790.5=14.90mL,0.21%(A)0.06%(B)0.11%(C),,(VT)0.6%33.3精密度的判断2.3(5)(6)(7),sdd0.00415mL(A)0.0177mL(B)0.0109mL(C),sdv(V)0.02880.05950.0467mL,0.19%0.40%0.31%,,sdv(V)(VT)0.5%33btheor(mL/g)bobs(mL/g)(%)aobs(mL)(%)sdd(mL)sdv(V)(mL)(%)A29.7929.67-0.40-0.03138-0.210.004150.02880.19B29.7929.68-0.37-0.0008251-0.060.01770.05950.40C29.7929.65-0.470.016120.110.01090.04670.313.4方法限度的确定3.13.23.3,,(0.1015moL/L)()(),,(6)11(),,6,1.2,,,4,(RSD)262010,44(9):24~27/,(x)11(),4ami(g)Vi(mL)xi(%)xtheor(%)x(%)xtheor(%)RSD(%)x(%)A10.502314.9199.6499.9799.50100.000.14-0.5020.501114.8699.54100.0130.498814.8199.66100.0040.502314.8799.3799.9750.499114.7799.33100.0160.501714.8799.49100.02B10.499514.94100.40100.0699.8499.990.34-0.1520.502514.9099.53100.0030.497914.7899.5799.9840.502014.9299.7699.9650.498314.8099.6999.9660.502214.98100.1299.99C10.501914.8499.2499.9899.7499.990.42-0.2520.497614.8099.8399.9730.498714.90100.28100.0240.502214.8699.3299.9950.498914.88100.1199.9860.502414.9299.68100.02:a4,,,,HPLCHPLC,,,,,HPLC,,,,10mL,,,,2.4(8):[1].[S].[2].[S].[3].[S].[4].[S].[5]EuropeanDirectoratefortheQualityofMedicines&HealthCare.TechnicalGuidefortheElaborationofMonographs[M].4thed,France:CouncilofEurope,2005:67-69.[6].[M].:,2005:96.[7].2010[M].:,2010:335-336.[8]TheUnitedStatesPharmacopeialConvention.The32ndRevisionoftheUnitedStatesPharmacopeia(USP32)andthe27thEditionoftheNationalFormulary(NF27)[M].Rockville:TwinbrookParkway,2008:2460.[9]BritishPharmacopoeiaCommission.BritishPharmacopoeia2009[M].London:BritishPharmacopoeiaCommissionOffice,2008:1174-1177.[10]TheCommitteeonJapanesePharmacopoeia.JapanesePharmaco-poeia[M].15thed.Tokyo:theCommitteeonJapanesePharmaco-poeia,2006:690-691.272010,44(9):24~27/,