乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座

乙醇檢測(cè)在試劑和藥典中應(yīng)用斯百全化學(xué)（上海）有限企業(yè)SpectrumChinaLtd.Spectrum質(zhì)檢部800.720.5720乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第1頁(yè)乙醇C2H6O46.07Ethanol.

EthylalcoholCAS#:[64-17-5].應(yīng)用：飲料汽車(chē)燃料消毒劑有機(jī)合成原料溶劑稀釋劑萃取劑洗滌劑乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第2頁(yè)Spectrum乙醇品種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:酒精純度,一個(gè)酒精純度相當(dāng)于0.5％酒精含量.乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第3頁(yè)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乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第4頁(yè)GB/T678-無(wú)水乙醇乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第5頁(yè)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%乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第6頁(yè)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%乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第7頁(yè)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乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第8頁(yè)乙醇含量檢測(cè)應(yīng)用相對(duì)密度法

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

蒸餾法 USP<611>,MethodⅠ. 中國(guó)藥典版一部：附錄ⅨM乙醇量測(cè)定法Ⅱa,b,c氣相色譜法（GC） USP<611>,Alcoholdetermination,MethodⅡ. BE115,BelladonnaTincture ACS10th,Ethylalcohol. HP612，ReagentAlcohol,Denatured,ExceedsA.C.S.Specifications,HPLCGrade USP<467>,Residualsolvents,class3. 中國(guó)藥典版二部：附錄ⅦE乙醇量測(cè)定法 中國(guó)藥典版一部：附錄ⅨM乙醇量測(cè)定法Ⅰ乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第9頁(yè)相對(duì)密度法-USP<841>,SpecificGravity,methodⅠET107,Dehydratedalcohol,200proof,undenatured,USPAlcoholcontent:≧99.2%,byweight;≧99.5%,byvolume,at15.56℃.原理:25℃下,相同體積乙醇和水重量比值,折算成15.56℃下乙醇重量含量或體積含量.方法:使用同一比重瓶，先將先將一定體積燒開(kāi)過(guò)蒸餾水放入其中,分別稱(chēng)量25℃下空瓶和水裝入后總重量,兩者之差就是25℃下水重量.同理測(cè)量25℃下乙醇重量.乙醇和水重量比為25℃下乙醇比重.經(jīng)過(guò)查找USPreferencetable–Alcoholometrictable中數(shù)據(jù)，確定15.56℃下乙醇體積含量或者重量含量.比重瓶乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第10頁(yè)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乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第11頁(yè)蒸餾法-USP<611>,MethodⅠ

中國(guó)藥典版一部：附錄ⅨM乙醇量測(cè)定法Ⅱ適用范圍USP<611>,MethodⅠ:流浸膏劑,酊劑中國(guó)藥典版一部：附錄ⅨM乙醇量測(cè)定法Ⅱ:流浸膏劑,酊劑,中藥制劑原理依據(jù)樣品不一樣性質(zhì),加入不一樣物質(zhì),進(jìn)行預(yù)處理.蒸餾,取得乙醇餾出物.測(cè)定蒸餾物相對(duì)密度,折算出乙醇含量.方法(中國(guó)藥典版一部：附錄ⅨM乙醇量測(cè)定法Ⅱ)Alcoholcontent≦30%:稱(chēng)取20℃下樣品25ml,置于150-200ml蒸餾瓶中,加水約25ml,蒸餾.待餾出物達(dá)23ml時(shí),停頓蒸餾.加水至刻度,測(cè)量乙醇在20℃下相對(duì)密度,計(jì)算出乙醇含量;Alcoholcontent﹥30%:稱(chēng)取20℃下樣品25ml,置于150-200ml蒸餾瓶中,加水約50ml,蒸餾.待餾出物達(dá)48ml時(shí),停頓蒸餾.加水至刻度,測(cè)量乙醇在20℃下相對(duì)密度,計(jì)算出乙醇含量;樣品含有揮發(fā)性物質(zhì),如揮發(fā)油,三氯甲烷,乙醚,樟腦等.可先加入氯化鈉使之飽和,后加入乙醚,使溶液分層,取水層按常規(guī)檢測(cè).樣品含有游離氨或揮發(fā)性酸.可先加入稀硫酸或氫氧化鈉溶液,調(diào)整酸堿度,再按常規(guī)檢測(cè).乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第12頁(yè)蒸餾法-USP<611>,MethodⅠ

B1068,BenzalkoniumChlorideSolution,50Percent,NF

Alcoholcontent≦10.0%25℃下量取樣品25.0ml,加水100ml,365℃下蒸餾.餾出物大約23ml時(shí),停頓蒸餾,在25℃下定容到25ml.因餾出物渾濁,加入CaCO3振搖,過(guò)濾.使用10ml比重瓶測(cè)量25℃下乙醇比重,折算出乙醇含量.結(jié)果:乙醇餾出物比重@25℃:0.9938 乙醇含量:4.2%乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第13頁(yè)氣象色譜法(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乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第14頁(yè)HP612,ReagentAlcohol,Denatured,ExceedsA.C.S.Specification,HPLCGradeSpecifications,HPLCGrade乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第15頁(yè)氣相色譜法(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)乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第16頁(yè)BE115,BelladonnaTincture,AlcoholContent乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第17頁(yè)

氣相色譜法(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%乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第18頁(yè)SU124,SulfacetamideSodium,Monohydrate,USP,ResidualSolvents-Ethanol

乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第19頁(yè)中國(guó)藥典版一部：附錄ⅨM乙醇量測(cè)定法Ⅰ適用范圍：測(cè)定制劑中在20℃時(shí)乙醇含量（%，ml/ml）色譜條件與系統(tǒng)適應(yīng)性試驗(yàn)：用鍵合交聯(lián)聚乙二醇為固定液毛細(xì)管柱；起始溫度為50℃，維持7分鐘，再以每分鐘10℃速率升溫至110℃；進(jìn)樣口溫度190℃；FID檢測(cè)器溫度220℃。理論板數(shù)按正丙醇峰計(jì)算應(yīng)不低于8000，乙醇峰與正丙醇峰分離度應(yīng)大于2.0.校正因子測(cè)定：精密量取恒溫至20℃無(wú)水乙醇4ml、5ml、6ml，分別置100ml量瓶中，分別精密加入恒溫至20℃正丙醇（內(nèi)標(biāo)物質(zhì)）5ml，用水稀釋至刻度，搖勻，精密量取上述各溶液1ml，分別置100ml量瓶中，用水稀釋至刻度，搖勻（必要時(shí)可深入稀釋?zhuān)?，作為?duì)照品溶液。取上述三種溶液各適量，注入氣相色譜儀，分別連續(xù)進(jìn)樣3次，測(cè)定峰面積，計(jì)算校正因子，所得校正因子相對(duì)標(biāo)準(zhǔn)偏差不得大于2.0%。測(cè)定法：精密量取恒溫至20℃供試品適量（相當(dāng)于乙醇約5ml），置100ml量瓶中，精密加入恒溫至20℃正丙醇5ml，用水稀釋至刻度，搖勻，精密量取該溶液1ml，置100ml量瓶中，用水稀釋至刻度，搖勻（必要時(shí)可深入稀釋?zhuān)?，作為供試品溶液。?μl注入氣相色譜儀，測(cè)定，即得。乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第20頁(yè)CNAST0546能力驗(yàn)證

氣相色譜法測(cè)定藥品中乙醇含量樣品名稱(chēng):T1064盲樣方法:

中國(guó)藥典版一部：附錄ⅨM乙醇量測(cè)定法Ⅰ;或試驗(yàn)室慣用氣象色譜法能力驗(yàn)證結(jié)果試驗(yàn)結(jié)果:47.92%平均值:46.39%Z絕對(duì)值:7.12>3,不合格結(jié)果復(fù)測(cè)結(jié)果試驗(yàn)結(jié)果:46.23%平均值:46.39%Z絕對(duì)值:0.2﹤1,滿(mǎn)意結(jié)果乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第21頁(yè)原因分析檢測(cè)方法123樣品處理方法中國(guó)藥典中國(guó)藥典中國(guó)藥典色譜條件中國(guó)藥典中國(guó)藥典中國(guó)藥典進(jìn)樣方法直接進(jìn)樣頂空進(jìn)樣頂空進(jìn)樣計(jì)算方法非加標(biāo)非加標(biāo)加標(biāo)乙醇含量45.98%47.46%45.91%乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第22頁(yè)CNAST0546能力驗(yàn)證

氣相色譜法測(cè)定藥品中乙醇含量—直接進(jìn)樣乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第23頁(yè)CNAST0546能力驗(yàn)證

氣相色譜法測(cè)定藥品中乙醇含量—頂空進(jìn)樣乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第24頁(yè)CNAST0546能力驗(yàn)證

氣相色譜法測(cè)定藥品中乙醇含量—頂空進(jìn)樣乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第25頁(yè)總結(jié)方法偏離和確認(rèn)方法驗(yàn)證精密度準(zhǔn)確度專(zhuān)屬性線(xiàn)性?xún)x器比對(duì)人員比對(duì)方法比對(duì)試驗(yàn)室間比對(duì)乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第26頁(yè)小知識(shí)：Alcohol,Aldehyde-free無(wú)醛乙醇制備USP-Dissolve2.5gofleadacetatein5mLofwater,addthesolutionto1000mLofalcoholcontainedinaglass-stopperedbottle,andmix.Dissolve5gofpotassiumhydroxidein25mLofwarmalcohol,coolthesolution,andadditslowly,withoutstirring,tothealcoholsolutionofleadacetate.After1hourshakethemixturevigorously,allowittostandovernight,decanttheclearliquid,andrecoverthealcoholbydistillation.溶解2.5g醋酸鉛于5ml水中，將溶液加到裝有1000ml乙醇具塞玻璃瓶中，混合。溶解5g氫氧化鉀于25ml溫乙醇中，冷卻，將此溶液遲緩地加到醋酸鉛乙醇溶液中，不用攪拌。1小時(shí)后，猛烈振蕩該混合液，放置過(guò)夜，輕輕倒出澄清液體，蒸餾，得到無(wú)醛乙醇。EP-Mix1200mlofethanol(96%)with5mlofa40%w/vsolutionofsilvernitrateand10mlofacooled50%w/vsolutionofpotassiumhydroxide.Shake,allowtostandforafewdaysandfilter.Distilthefiltrateimmediatelybeforeuse.將1200ml乙醇和5ml40%硝酸銀溶液，以及10ml冷卻50%氫氧化鉀溶液混合。振蕩，放置數(shù)天后過(guò)濾。使用前蒸餾濾液，得到無(wú)醛乙醇。乙醇檢測(cè)在試劑和藥典中的應(yīng)用專(zhuān)家講座第27頁(yè)小知識(shí)：Alcohol,Neutralized中性乙醇制備USP—Toasuitablequantityofalcoholadd2or3dropsofphenolphthaleinTSandjustsufficient0.02Nor0.1Nsodiumhydroxidetoproduceafaintpinkcolor.Prepareneutralizedalcoholjustpriortouse.一定量乙醇中，加入2-3滴酚酞指