乙醇检测在试剂和药典中的应用专家讲座

乙醇检测在试剂和药典中应用斯百全化学（上海）有限企业SpectrumChinaLtd.Spectrum质检部800.720.5720乙醇检测在试剂和药典中的应用专家讲座第1页乙醇C2H6O46.07Ethanol.

EthylalcoholCAS#:[64-17-5].应用：饮料汽车燃料消毒剂有机合成原料溶剂稀释剂萃取剂洗涤剂乙醇检测在试剂和药典中的应用专家讲座第2页Spectrum乙醇品种A2176 Alcohol,Denatured,190ProofA1038 Alcohol,Anhydrous,CompletelyDenaturedA1040 ReagentAlcohol,Denatured,Reagent,ACSE1020 EthylAlcohol,190Proof,FCCE1028 EthylAlcohol,Absolute,200Proof,Reagent,ACSE1029 EthylAlcohol,190Proof,Reagent,ACSE1068 DehydratedAlcohol,200Proof,USP,EP,BPE1421 Alcohol,190Proof,BiotechGradeE1424 DehydratedAlcohol,200Proof,BiotechGradeET107 DehydratedAlcohol,200Proof,Undenatured,USPET108 Alcohol,190Proof,USPHP612 ReagentAlcohol,Denatured,ExceedsA.C.S.Specifications,HPLCGradeHS002 ReagentAlcohol,Denatured,HistologicalGradeEX0278 Alcohol,Denatured,OmniSolv(R)EX0289 EthylAlcohol,MultiPharm,200Proof,EP,JP,USPEX0290 EthylAlcohol,Pure,190Proof,HPLCGrade*Proof:酒精纯度,一个酒精纯度相当于0.5％酒精含量.乙醇检测在试剂和药典中的应用专家讲座第3页E1028,EthylAlcohol,Absolute,200Proof,Reagent,ACS

TEST SPECIFICATION

ASSAY(byVOLUME) 99.5%--COLOR(APHA) –10SOLUBILITYINWATER TOPASSTESTWATER --0.2%RESIDUEAFTEREVAPORATION --0.001%ACETONE TOPASSTEST(limitabout0.001%)ISOPROPYLALCOHOL TOPASSTEST(limitabout0.003%)TITRABLEACID --0.0005meq/gTITRABLEBASE --0.0002meq/gMETHANOL(CH3OH) --0.1%SUBSTANCESDARKENEDBY(H2SO4) TOPASSTESTSUBSTANCESREDUCINGPERMANGANATE TOPASSTEST乙醇检测在试剂和药典中的应用专家讲座第4页GB/T678-无水乙醇乙醇检测在试剂和药典中的应用专家讲座第5页A1040,ReagentAlcohol,Denatured,Reagent,ACSTEST SPECIFICATION

ASSAY:ETHANOL+METANOL(v/v) 94.0-96.0%ISOPROPANOL(v/v) 4.0-6.0%WATER --0.5%COLOR(APHA) –10RESIDUEAFTEREVAPORATION --0.001%乙醇检测在试剂和药典中的应用专家讲座第6页HP612,ReagentAlcohol,Denatured,ExceedsA.C.S.Specifications,HPLCGradeTEST

SPECIFICATION

ASSAY:ETHANOL+METANOL(v/v) 94.0-96.0%ISOPROPYLALCOHOL(v/v) 4.0-6.0%ULTRAVIOLETABSORBANCE(1cmcellvs.water)-- TOPASSTEST205nm 1.00210nm 0.65220nm 0.35230nm 0.20250nm 0.04270nm 0.01300nm ＜0.005COLOR(APHA) –10RESIDUEAFTEREVAPORATION --4PPMWATER --0.1%乙醇检测在试剂和药典中的应用专家讲座第7页E1068,DehydratedAlcohol,200Proof,USP,EP,BPTEST SPECIFICATION

ASSAY(byVOLUME) 99.5%--CLARITYOFSOLUTION TOPASSTESTCOLOROFSOLUTION TOPASSTESTACIDITYORALKALINITY TOPASSTESTRELATIVEDENSITY 0.790-0.793SPECIFICGRAVITY@15.56oC --0.7962UVABSORPTION TOPASSTESTVOLATILEIMPURITIES TOPASSTESTNONVOLATILERESIDUE TOPASSTESTIDENTIFICATION TOPASSTESTRESIDUALSOLVENTS TOPASSTEST乙醇检测在试剂和药典中的应用专家讲座第8页乙醇含量检测应用相对密度法

USP<841>,SpecificGravity. ET107,Dehydratedalcohol,200proof,undenatured,USP

蒸馏法 USP<611>,MethodⅠ. 中国药典版一部：附录ⅨM乙醇量测定法Ⅱa,b,c气相色谱法（GC） USP<611>,Alcoholdetermination,MethodⅡ. BE115,BelladonnaTincture ACS10th,Ethylalcohol. HP612，ReagentAlcohol,Denatured,ExceedsA.C.S.Specifications,HPLCGrade USP<467>,Residualsolvents,class3. 中国药典版二部：附录ⅦE乙醇量测定法 中国药典版一部：附录ⅨM乙醇量测定法Ⅰ乙醇检测在试剂和药典中的应用专家讲座第9页相对密度法-USP<841>,SpecificGravity,methodⅠET107,Dehydratedalcohol,200proof,undenatured,USPAlcoholcontent:≧99.2%,byweight;≧99.5%,byvolume,at15.56℃.原理:25℃下,相同体积乙醇和水重量比值,折算成15.56℃下乙醇重量含量或体积含量.方法:使用同一比重瓶，先將先将一定体积烧开过蒸馏水放入其中,分別称量25℃下空瓶和水装入后总重量,兩者之差就是25℃下水重量.同理測量25℃下乙醇重量.乙醇和水重量比为25℃下乙醇比重.经过查找USPreferencetable–Alcoholometrictable中数据，确定15.56℃下乙醇体积含量或者重量含量.比重瓶乙醇检测在试剂和药典中的应用专家讲座第10页USPreferencetable–Alcoholometrictable1234

5678percentage

specificgravity

percentage

specificgravity

byvolumnat15.56℃byweightat25℃at15.56℃

byvolumnat15.56℃byweightat25℃at15.56℃

10.800.99850.9985

5143.430.92690.932221.590.99700.9970

5244.370.92480.930232.390.99560.9956

5345.330.92280.928243.190.99410.9942

5446.280.92070.926254.000.99270.9928

5547.250.91850.924164.800.99140.9915

5648.210.91640.922075.610.99010.9902

5749.190.91420.919986.420.98880.9890

5850.170.91200.917797.230.98750.9878

5951.150.90980.9155108.050.98620.9866

6052.150.90760.9133118.860.98500.9854

6153.150.90530.9111129.680.98380.9843

6254.150.90300.90881310.500.98260.9832

6355.170.90060.90651411.320.98140.9821

6456.180.89830.90421512.140.98020.9810

6557.210.89590.90191612.960.97900.9800

6658.240.89360.89951713.790.97780.9789

6759.280.89110.89721814.610.97670.9779

6860.330.88870.89481915.440.97560.9769

6961.380.88620.89232016.270.97440.9759

7062.440.88370.88992117.100.97330.9749

7163.510.88120.88742217.930.97210.9739

7264.590.87870.88482318.770.97100.9729

7365.670.87610.88232419.600.96980.9719

7466.770.87350.87972520.440.96850.9708

7567.870.87090.87712621.290.96730.9697

7668.980.86820.87452722.130.96610.9687

7770.100.86550.87182822.970.96480.9676

7871.230.86280.86912923.820.96350.9664

7972.380.86000.86643024.670.96220.9653

8073.530.85720.8636乙醇检测在试剂和药典中的应用专家讲座第11页蒸馏法-USP<611>,MethodⅠ

中国药典版一部：附录ⅨM乙醇量测定法Ⅱ适用范围USP<611>,MethodⅠ:流浸膏剂,酊剂中国药典版一部：附录ⅨM乙醇量测定法Ⅱ:流浸膏剂,酊剂,中药制剂原理依据样品不一样性质,加入不一样物质,进行预处理.蒸馏,取得乙醇馏出物.测定蒸馏物相对密度,折算出乙醇含量.方法(中国药典版一部：附录ⅨM乙醇量测定法Ⅱ)Alcoholcontent≦30%:称取20℃下样品25ml,置于150-200ml蒸馏瓶中,加水约25ml,蒸馏.待馏出物达23ml时,停顿蒸馏.加水至刻度,测量乙醇在20℃下相对密度,计算出乙醇含量;Alcoholcontent﹥30%:称取20℃下样品25ml,置于150-200ml蒸馏瓶中,加水约50ml,蒸馏.待馏出物达48ml时,停顿蒸馏.加水至刻度,测量乙醇在20℃下相对密度,计算出乙醇含量;样品含有挥发性物质,如挥发油,三氯甲烷,乙醚,樟脑等.可先加入氯化钠使之饱和,后加入乙醚,使溶液分层,取水层按常规检测.样品含有游离氨或挥发性酸.可先加入稀硫酸或氢氧化钠溶液,调整酸碱度,再按常规检测.乙醇检测在试剂和药典中的应用专家讲座第12页蒸馏法-USP<611>,MethodⅠ

B1068,BenzalkoniumChlorideSolution,50Percent,NF

Alcoholcontent≦10.0%25℃下量取样品25.0ml,加水100ml,365℃下蒸馏.馏出物大约23ml时,停顿蒸馏,在25℃下定容到25ml.因馏出物浑浊,加入CaCO3振摇,过滤.使用10ml比重瓶测量25℃下乙醇比重,折算出乙醇含量.结果:乙醇馏出物比重@25℃:0.9938 乙醇含量:4.2%乙醇检测在试剂和药典中的应用专家讲座第13页气象色谱法(GC)-ACS10th:EthylAlcohol. HP612,ReagentAlcohol,Denatured,ExceedsA.C.S.Specification,HPLCGradeSpecifications,HPLCGrade

Application:EthylAlcoholcontent≧95.0%GCmethodColumn:methylsiliconecapillaryColumntemperature:40℃for5min,programmedto220℃at10℃/min,hold2minInjectortemperature:150-220℃Detectortemperature:250℃Samplesize:0.2μlsplitlessCarriergas:heliumat3ml/minDetector:TCDMeasuretheareaunderallpeaks,andcalculatetheethylalcoholcontentinareapercent乙醇检测在试剂和药典中的应用专家讲座第14页HP612,ReagentAlcohol,Denatured,ExceedsA.C.S.Specification,HPLCGradeSpecifications,HPLCGrade乙醇检测在试剂和药典中的应用专家讲座第15页气相色谱法(GC)-USP<611>,Alcoholdetermination,MethodⅡa.BE115,BelladonnaTincture

Application:Alcoholcontent:65.0%-70.0%.Column:DB-624Columntemperature:120℃,Injectortemperature:210℃Detectortemperature:210℃Samplesize:5μlCarriergas:nitrogenorheliumDetector:FIDStandardsolution:5mleachUSPAlcoholRSandUSPacetoneRStogetherdilutedbywaterto50ml.Teststocksolution:Dilutesamplestepwisetogeta2%alcoholsolution.Testsolution:5mleachteststocksolutionandUSPacetoneRStogetherdilutedbywaterto50ml.SystemSuitabilityTest:R≧2(alcoholtoacetone)tailingfactor:≦2.0(alcohol)RSD≦2.0%(ratioofalcoholtoacetone)乙醇检测在试剂和药典中的应用专家讲座第16页BE115,BelladonnaTincture,AlcoholContent乙醇检测在试剂和药典中的应用专家讲座第17页

气相色谱法(GC)-USP<467>ResidualSolvents

Application:Alcoholcontent:﹤5000ppm.Column:DB-624Columntemperature:40℃for20min,programmedto240℃at10℃/min,hold20minInjectortemperature:140℃Detectortemperature:250℃Samplesize:5ml,headspaceCarriergas:heliumDetector:FIDSplitratio:5:1SystemSuitabilityTest:R﹥1.0RSD≦2.0%乙醇检测在试剂和药典中的应用专家讲座第18页SU124,SulfacetamideSodium,Monohydrate,USP,ResidualSolvents-Ethanol

乙醇检测在试剂和药典中的应用专家讲座第19页中国药典版一部：附录ⅨM乙醇量测定法Ⅰ适用范围：测定制剂中在20℃时乙醇含量（%，ml/ml）色谱条件与系统适应性试验：用键合交联聚乙二醇为固定液毛细管柱；起始温度为50℃，维持7分钟，再以每分钟10℃速率升温至110℃；进样口温度190℃；FID检测器温度220℃。理论板数按正丙醇峰计算应不低于8000，乙醇峰与正丙醇峰分离度应大于2.0.校正因子测定：精密量取恒温至20℃无水乙醇4ml、5ml、6ml，分別置100ml量瓶中，分別精密加入恒温至20℃正丙醇（内标物质）5ml，用水稀释至刻度，摇匀，精密量取上述各溶液1ml，分別置100ml量瓶中，用水稀释至刻度，摇匀（必要时可深入稀释），作为对照品溶液。取上述三种溶液各适量，注入气相色谱仪，分別连续进样3次，测定峰面积，计算校正因子，所得校正因子相对标准偏差不得大于2.0%。测定法：精密量取恒温至20℃供试品适量（相当于乙醇约5ml），置100ml量瓶中，精密加入恒温至20℃正丙醇5ml，用水稀释至刻度，摇匀，精密量取该溶液1ml，置100ml量瓶中，用水稀释至刻度，摇匀（必要时可深入稀释），作为供试品溶液。取1μl注入气相色谱仪，测定，即得。乙醇检测在试剂和药典中的应用专家讲座第20页CNAST0546能力验证

气相色谱法测定药品中乙醇含量样品名称:T1064盲样方法:

中国药典版一部：附录ⅨM乙醇量测定法Ⅰ;或试验室惯用气象色谱法能力验证結果试验结果:47.92%平均值:46.39%Z绝对值:7.12>3,不合格结果复测结果试验结果:46.23%平均值:46.39%Z绝对值:0.2﹤1,满意结果乙醇检测在试剂和药典中的应用专家讲座第21页原因分析检测方法123样品处理方法中国药典中国药典中国药典色谱条件中国药典中国药典中国药典进样方法直接进样顶空进样顶空进样计算方法非加标非加标加标乙醇含量45.98%47.46%45.91%乙醇检测在试剂和药典中的应用专家讲座第22页CNAST0546能力验证

气相色谱法测定药品中乙醇含量—直接进样乙醇检测在试剂和药典中的应用专家讲座第23页CNAST0546能力驗證

气相色谱法测定药品中乙醇含量—顶空进样乙醇检测在试剂和药典中的应用专家讲座第24页CNAST0546能力驗證

气相色谱法测定药品中乙醇含量—顶空进样乙醇检测在试剂和药典中的应用专家讲座第25页总结方法偏离和确认方法验证精密度准确度专属性线性仪器比对人员比对方法比对试验室间比对乙醇检测在试剂和药典中的应用专家讲座第26页小知识：Alcohol,Aldehyde-free无醛乙醇制备USP-Dissolve2.5gofleadacetatein5mLofwater,addthesolutionto1000mLofalcoholcontainedinaglass-stopperedbottle,andmix.Dissolve5gofpotassiumhydroxidein25mLofwarmalcohol,coolthesolution,andadditslowly,withoutstirring,tothealcoholsolutionofleadacetate.After1hourshakethemixturevigorously,allowittostandovernight,decanttheclearliquid,andrecoverthealcoholbydistillation.溶解2.5g醋酸铅于5ml水中，将溶液加到装有1000ml乙醇具塞玻璃瓶中，混合。溶解5g氢氧化钾于25ml温乙醇中，冷卻，將此溶液迟缓地加到醋酸铅乙醇溶液中，不用搅拌。1小时后，猛烈振荡该混合液，放置过夜，轻轻倒出澄清液体，蒸馏，得到无醛乙醇。EP-Mix1200mlofethanol(96%)with5mlofa40%w/vsolutionofsilvernitrateand10mlofacooled50%w/vsolutionofpotassiumhydroxide.Shake,allowtostandforafewdaysandfilter.Distilthefiltrateimmediatelybeforeuse.將1200ml乙醇和5ml40%硝酸银溶液，以及10ml冷卻50%氢氧化钾溶液混合。振荡，放置数天后过滤。使用前蒸馏滤液，得到无醛乙醇。乙醇检测在试剂和药典中的应用专家讲座第27页小知识：Alcohol,Neutralized中性乙醇制备USP—Toasuitablequantityofalcoholadd2or3dropsofphenolphthaleinTSandjustsufficient0.02Nor0.1Nsodiumhydroxidetoproduceafaintpinkcolor.Prepareneutralizedalcoholjustpriortouse.一定量乙醇中，加入2-3滴酚酞指