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1、學(xué)報(bào)JournalofChinaPharmaceuticalUniversity2006,37(2):153-156153HPLC法測(cè)定大鼠血漿和膽汁中安妥沙星濃度及其藥代動(dòng)力學(xué)X胡婕慧,謝林,劉曉東(中國(guó)藥科大學(xué)藥物代謝與動(dòng)力學(xué)研究中心,南京210009)摘要目的:建立大鼠血漿和膽汁中安妥沙星濃度的HPLC2UV測(cè)定方法。方法:樣品經(jīng)高氯酸處理后進(jìn)行HPLC2TMUV分析。色譜柱DiamonsilC18(5μm,150mm×416mmID),流動(dòng)相:0105mol/LKH2PO4(pH=3)2乙腈2三乙胺(84∶16∶114),流速:
2、115mL/min,紫外檢測(cè)波長(zhǎng):297nm。測(cè)定大鼠靜脈注射安妥沙星715mg/kg后的血藥濃度變化和膽汁累積排泄率。結(jié)果:安妥沙星在血漿中的線性范圍為011~1218μg/mL,在膽汁中的線性范圍為011~2516μg/mL,定量下限(LLOQ)均為011μg/mL,日內(nèi)和日間RSD均小于15%,準(zhǔn)確度(relativeerror,RE)為-3101%~7150%。血漿中回收率大于70%,膽汁中回收率大于90%。大鼠靜注715mg/kg安妥沙星后AUC0-6為(313175±47128)μg·min/mL,t1/2為(122103±
3、23103)min,CL為(20106±4184)mL/(kg·min),6h膽汁累積排泄率為(3103±0143)%。結(jié)論:該方法經(jīng)考察符合生物樣品的測(cè)定要求,可應(yīng)用于大鼠體內(nèi)安妥沙星血液和膽汁中濃度的測(cè)定和藥代動(dòng)力學(xué)研究,膽汁排泄為安妥沙星一條重要的消除途徑。關(guān)鍵詞安妥沙星;HPLC;藥代動(dòng)力學(xué);膽汁排泄中圖分類(lèi)號(hào)R969.1文獻(xiàn)標(biāo)識(shí)碼A文章編號(hào)1000-5048(2006)02-0153-04DeterminationofantofloxacininratplasmaandbilebyHPLCandstudyofitspharma
4、cokineicsHUJie2hui,XIELin,LIUXiao2dongCenterofDrugMetabolismandPharmacokinetics,ChinaPharmaceuticalUniversity,Nanjing210009,ChinaAbstractAim:TodevelopanHPLC2UVmethodtoassesstheconcentrationofantofloxacininratplasmaandbile.Methods:Afterantofloxacinwasintravenouslyatadoseo
5、f715mg/kgtorats,bloodandbilesampleswerecollected.TMFollowingproteinprecipitationwithHClO4,theanalyteswereseparatedonaDiamonsilC18(5μm,150mm×416mmID)columnwithamobilephaseconsistingof0105mol/Lphosphatebuffer(pHadjustedto310)2acetonitrile2triethy2lamine(84∶16∶114)ataflowra
6、teof115mL/minandtheeluentwasdetectedat297nm.Results:Linearcalibrationwasgeneratedoveraconcentrationrangeof011~1218μg/mLforplasmasamplesand011~2516μg/mLforbilesamples,respectively.Intra2andinter2daysprecisionandaccuracywereacceptableforallqualitycontrolsampleswithrelative
7、errorrangingfrom-3101%to7150%,includingbothlowerlimitofquantification(LLOQ)of011μg/mL.Themeanrecoveryofantofloxacinfromplasmaandbilewasabove70%and90%,respectively.Pharmacokineticpa2rameterswereestimatedasfollows:AUC0-6(313175±47128)μg·min/mL,t1/2(122103±23103)minandCL(20
8、106±4184)mL/(kg·min).Thecumulativebiliaryexcretionfor6hoursafteradministrationwas(3103±0143)%ofthedose.