硫酸核糖霉素的质量研究

华中科技大学硕士学位论文硫酸核糖霉素的质量研究姓名：李晓鑫申请学位级别：硕士专业：药物分析学指导教师：马长清;姜红20080515_____1::[1-2]HPLC-UV2005[3][4]TLC,HPLC-ELSDHPLC-ELSDWHOG2-----10123820.2%211020minHPLC-ELSDHPLC-ELSDDionexAcclaimC184.6mm250mm,5µm0.8%20mmol/L-5545-3.9893µg/ml~35.904µg/mlr=0.9995HPLC-ELSD56HPLC-ELSDHPLC-ELSDHPLC-ELSDGC19;;;;-;;3StudiesonQualityforRibostamycinSulfateCandidate:LiXiaoxinSupervisor:MaChangqingJiangHongAbstractThispaperstudiesonqualityforRiobostamycinSulfate,whichisoneoftheaminoglycosideantibiotics.TLCwasemployedtodetecttherelatedsubstanceinRiobostamycinSulfate,andanewdetector–ELSD(EvaporativeLightScatteringDetector),asatisfactorymethodforthedeterminationofRiobostamycinwasestablished..AndthispaperdidaseriesofworktosetuptherefrencesubstanceofRiobostamycin.ThewholeworkwaspreparedforthenewChinaPharmacopoeia.Thefollowingworkshavebeendoneinthispaper.First,therewerefewreportsabouttherelatedsubstancesinRiobostamycinSulfateoverabroad.ThispaperhastriedtimestoestablishabestTLC.TodeveloponthesilicaGplate,thedevelopingsolventis2-butanone-methanol-isopropanol-ammoniawaterstronger-water(10:12:3:8:2)andcoloredby0.2%triketohydrindenehydratewhichdissolvedinthen-butanolwhichsaturatedbywater.Themethodissimpleforthequalitycontrolofthepreparation,andhasagoodspecificity.Then,anewdetector-ELSDwasestablishedtodetectrelatedsubstancesinRiobostamycinSulfate.DionexAcclaimC18(4.6mm250mm,5µm)columnasstationaryphase,20mmol/Lammoniumacetatesolution(concluding0.8%pentafluoropropionicacid)andmethanol(55:45)asmobilephase,detectedwithEvaporativeLight–ScatteringDetector.Theestablishedmethodoftherelativesubstancedetectionhadgoodlinearitywithintherangeof3.9893µg/ml~35.904µg/ml(r=0.9995).4Second,forthedeterminationofthecontentofRiobostamycinSulfate,5batchesofRiobostamycinSulfateand6batchesofRiobostamycinSulfateforInjectionweredeterminedwithHPLC-ELSDandmicrobialassayrespectively.TheconcentdetectedbymicrobialassaywashigherthanHPLC-ELSDThisshowedtheHPLC-ELSDcanremovetheinterferenceofNeamine,andHPLC-ELSDwasmorerigorousandbetterthanmicrobialassay.Third,setupthereferencesubstanceofRiobostamycinwiththerulesaboutthesingleantibiotics.Aftersubtractingtheorganicadmixture,moisturecontent,evaporatorcomponentandashcontent,theprincipalconstituentwasthepurityofRiobostamycin.KeywordsRiobostamycinSulfate;Neamine;relatedsubstance;TLC;HPLC-ELSD;establishmentofreferencesubstance;GC5[1-2](Ribostamycin)1984[5-7][8]2005[3][4]HPLC-UV[9]-HPLC-ELSD20101HPLC-ELSD200562005l19P.J.Claes[10-11]TLCpH[12]2-----10123820.2%11020min(2010)EvaporativeLight-ScatteringDetector,ELSD[13-14][15-18][19-22][23-25][26-29][30-33][34][35-36][37-38]HPLC-ELSDHPLC-ELSD[39]7[40-41]G.InchausepeHPLC-MS[42]HPLC-[39][43]2346--2-26-/-/-[39][43]2346--2-26-2HPLC-ELSDHPLC-ELSDHPLC1HPLC-ELSDHPLC-ELSDHPLC-ELSD83911.13489301695u/mg130411-200307ABCDEF2-USAG10µl1.21.2.1G0.5%130.3mm,1052h,1.2.22-----10123821.2.31.2.3.10.3g1ml20mg101.2.3.21ml0.4mg1ml1mg11ml1mg21ml20mg1.2.41.2.4.10606281g/100720mg695u/mg500mg25ml1mol/LHCL2ml,10min1mol/LNaOH2ml2.4.1.11mol/LNaOH5ml,10min,1mol/LHCL5ml2.4.1.13%H2O25ml,10min,2.4.1.130min,1.2.4.2(2005VB)2µlG2-----10123820.2%11020min1.1111.2.3.0606281g/1004.5.6.7.11.2.4.31ml0.2mg0.2µl0.4µl1µl2µl20.08µg12345671221.0.2µl2.0.4µl3.1µl4.2µl1.2.4.41.2.3.11ml0.4mg112ml2ml1ml0.2mg21ml0.6mg332ml1ml1ml0.4mg4;32ml4ml1ml0.2mg51ml1mg62µl,1.2.4.211234131mg/mlmg/ml0.63%0.42%0.21%0.42%0.21%A0606281g/10020.2B200104031g/10030.4C200506520.5g/5020.40.2D0606011g/10020.40.2E0606010.5g/5020.40.2F0606020.5g/5020.40.2B(200104033%2%2%1%1.31.3.12005[8]1412005---8.8%25151040210%-11[44]3--25232[45]42----108.537RfRf0.152----1010374Rf0.262----101138335Rf0.2372-----10%108.53710Rf82-----10113828RfRf0.3RfRf10%Rf0.42-----101238215361.2.3.4.5.6.7.8.9.1.3.22µg1230.02g50ml10ml0.2%0.50.50.513232pH5~72123456789160.2%HPLC-ELSD2HPLC-ELSD2.12.1.13489301695u/mg130411-200307pentafluoropropionicacid,97%,ProductofGB,NewJersey,USA2.1.2DionexP680AlltechELSD20000.8%20mmol/L-55450.8ml/minDionexAcclaimC184.6mm250mm,5µm30110N299.99%N22.6L/min12.1.32.1.3.10606280.0724g25mlUV365nm48h170.0725g25ml1001h,0.0726g25ml1mol/L5ml10030s,1mol/L5ml0.0722g25ml1mol/L5ml10020min,1mol/L5ml0.0723g25ml3%H2O25ml10020min,0.0718g25ml20µl34~133minmin10.804282112.1210.764254012.1110.804281912.1310.875395711.8410.796265812.1310.867335512.13180.02.55.07.510.012.515.017.520.022.0-15255075100130#6[modifiedbyy1]ELSDmVmin3.3914.8635.0896.58710.80112.12440.02.55.07.510.012.515.017.520.022.0-15255075100130#11[modifiedbyy1]ELSDmVmin3.3414.8655.0896.58310.75612.10550.02.55.07.510.012.515.017.520.022.0-15255075100130#10[modifiedbyy1]ELSDmVmin3.3904.8615.0906.58410.80112.1286190.02.55.07.510.012.515.017.520.022.0-15255075100130#13[modifiedbyy1](10030s)ELSDmVmin3.3024.0784.8335.0676.52810.77412.00170.02.04.06.08.010.012.015.0-15255075100130#8[modifiedbyy1]ELSDmVmin3.3044.0874.8395.0856.5339.02710.78812.12680.02.55.07.510.012.515.017.520.022.0-15255075100130#9[modifiedbyy1]ELSDmVmin3.3884.7955.0716.1866.5617.7608.4779.76910.86012.1299200.02.04.06.08.010.012.015.0-15255075100130#3[modifiedbyy1]ELSDmVm