液相色谱2串联质谱法在药物代谢研究中应用最新进展

21,2,2,2(1,010050;2,110179)[]2,,2,,,,,[];;[]R917.4;R974[]A[]1003-3734(2007)23-1981-06RecentprogressontheapplicationofLC2MS2MSindrugmetabolismGUOZhi1,ZHANGXuan2,SONGDong2Mei2,WANGLian2(1TheAffiliatedHospitalofMongoliaMedicalCollege,Huhehaote010050,China;2ShenyangE2livingpharmaceuticalCo.Ltd,Shenyang110179,China)[Abstract]Theliquidchromatography2tandemmassspectrometrywasanimportanttechnologyofmodernseparationandanalysisbecauseofitshighseparatingpower,highsensitivity,highspecificityandwiderangeofapplication.Comparedwithsinglemassspectrometry,thetandemmassspectrometrywasmoresensitiveandselective,anditcanprovidemoreabundantinformationaboutmolecularstructure.Firstly,thispaperexplainedthefundamentalprincipleoftandemmassspectrometry,commonmassanaly2zeranditscharacteristic,differenttandemmodeoftandemmassspectrometryanddataacquisitionoftheliquidchromatography2tandemmassspectrometry.Secondly,theauthorintroduceditslatestprogressiveapplicationinthedrugmetabolism,suchasdeterminationofthepharmacokineticsparameterofthedrugusingtandemmassspectrometry,identificationofthedrugmetabolitesusingvarioustandemmassmode,sumofthefitandunfitofeachmode,applicationstrategyoftheidentificationofthedrugmetabolites,andprospectsfortheapplicationinthedrugmetabolisminthefuture.[Keywords]liquidchromatography;tandemmassspectrometry;drugmetabolism2(LC/MS),LC,MS,,,,,,,,,2(LC2MSn)1(MS/MS)1.1:(EI)1891ChineseJournalofNewDrugs2007,Vol.16No.2320071623(CI)(FAB)(FI)(FD)(API)(MALDI)(ICP)(API),(ESI)(APCI)(APPI)API,,,ESI,,,ESI2MS,(CID);()(CID),1.2,:,,,,,,,(5ppm),(Q):,(DC)(RF),,,DCRF,(TRAP):,(RF),()RF,,,RF,,,(MSn)(TOF):,,,,,,,TOF,,MALDI2(FT2ICRMS):,,,,,,,,,1.3,,,B,E,:(:BEB,EBE,BEBE;:Q2Q2Q;:BE2QQ2TOFEBE2TOF):,Q2TRAP1.4,,MS,(N2Ar),MS,(QQQ)2891ChineseJournalofNewDrugs2007,Vol.16No.2320071623MS1MS2,MS1,MS21.54::CID,MS2(ESI,CI,FD,FAB),,/,:MS2,MS1,:MS1MS2,MS2MS1()Am,(Am),18Da2H2OII,(2176Da)(280Da),(GSH)(2129Da)(MRM)(SRM):MS1,,,MS1MS2,,2MS1,,3,,42()2.1,QQQ,,(MRM),m1,,m2m1m23:LC,MSm1,MSm2,,,,Su2ryawanshi[1]MRM4;[2]MRM;[3]MRM,2.2,,,,,,Yost[4],:,,,,.,2.2.1QQQ,,,III(12),[5]2,MRM53891ChineseJournalofNewDrugs2007,Vol.16No.23200716231I[6](Da)+16Ar2HAr2OHR2CH2R2CHOHN2R2NH2CO2RR2NOH2CO2RR2CH=CH2RR2CHOCH2RR2S2RR2SO2R-14N2R2NH2CH3R2NH2O2R2O2CH3R2OHS2R2S2CH3R2SH-30R2NO2R2NH2-2R2CH22OHR2COH+16R2COHR2COOH+14R2CH22OHR2COOH2II[6](Da)+176R2OHR2O2GluR2COOHR2COO2GluR2SHR2S2GluR2NH2R2NH2Glu+80R2OHR2OSO3HAr2NH2Ar2NH2SO3H+309R2CH=CH2R2CH22CH22S2G+162R2CH=CH2R2CH22CH22S2MercapturicAcid+309Ar2OAr2(OH)2S2G+162Ar2OAr2(OH)2S2MercapturicAcid+262R2CH22NO2R2CH22S2G+57+71+107R2COOHR2CO2AA+114+145QQQ,[7]QQQ,,,(DP),2.2.2TRAPQ2TRAPQQQ,TRAPMSMS/MS,(MSn),[8]HPLC2ESI2ITMSn,CIDMSn,,,31,II[9]HPLC2MSn,,,CIDMSn,MSnTRAP(1/3),Q2TRAP,Q2TRAP,QQQ3Q,2(Q2LIT)62[10],Q2LIT[11-12]2.2.3Q2TOFQ2TOFCID,,MRM[13]Q2TOF322,Q2TOF[14],epothiloneB[15],[16],III[17],ethoxidine[18]2.2.4QQQ,,,,,,Q2TOF,,QQQQ2TOFCID,Q2TRAP,,CID2.2.5Clarke[19]:QQQQ2TOFMS/MS,4891ChineseJournalofNewDrugs2007,Vol.16No.2320071623,QQQQ2LIT,QQQQ2LITMS/MSQ2TRAPMSn,,Q2TOF,,,LC/MSLC/MS/MSNMR2.2.6,[20]LC2NMR[21]/[22],[23][24],(stableisotope2labelling,SIL),,,MS,,[25],(),MSn[32S][34S]11,,[23][13C2215N][24],,MS,3Da,123,Lubman[26]TRAP2TOF,,Wysochi[27]2TOF,CID(SID)FT2ICRMSTOF,,[](1965-),,,,,,:[phone],E2mail:[e-mail][](1974-),,,:[phone][][1]SURYAWANSHIS,ASTHANARK,GUPTARC.Simultaneousestimationofmangiferinandfoursecoiridoidglycosidesinratplasmausingliquidchromatographytandemmassspectrometryanditsapplicationtopharmacokineticstudyofherbalpreparation[J].JChromatogrBAnalytTechnolBiomedLifeSci,2007,858(12):211-219.[2],,,.HPLC2MS/MS[J].,2007,28(5):73-77.[3],,,.2[J].,2007,16(2):81-84.[4]LEEMS,YOSTRA.Rapididentificationofdrugmetaboliteswithtandemmassspectrometry[J].BiomedEnvironMassSpectrom,1988,15(4):193-202.[5],.2[J].,2006,11(9):53-54.[6]WILFRIEDMAN.LiquidChromatography2MassSpectrometry[M].ThirdEdition.TaylorandFrancisGroupCRCPress,2006:258-259.[7],,,.LC2MS/MS[J].,2006,15(9):712-715.[8],,,.HPLC2ESI2ITMSn[J].,2005,40(9):838-841.[9],,,.2[J].,2006,41(5):467-470.[10]QIAOJP,ABLIZZ,CHUFM,etal.ApplicationofanovelQ2LIT2MStostudythemetabolismof62aminobutylphthalideinratbrains[J].RapidCommunMassSpectrom,2004,18(8):3142-3148.[11]LIAC,ALTOND,BRYANTMS,etal.Simultaneouslyquantif2yingparentdrugsandscreeningformetabolitesinplasmaphar2macokineticsamplesusingSRM2DDAonaQTrapinstrument[J].RapidCommunMassSpectrom,2005,19(6):1943-1949.[12]SHOUWZ,MAGISL,LIAC,etal.AnovelapproachtoperformmetabolitescreeningduringthequantitativeLC2MS2MSanalysesofinvitrometabolicstabilitysamplesusingaQ2LIT2MS[J].JMassSpectrom,2005,40(7):1347-1352.[13],,,.222[J].,2004,25(2):69-72.(1989)5891ChineseJournalofNewDrugs2007,Vol.16No.2320071623,,,,,,18500mg,2AUCCmax:2(P0.05),;(P0.05),[](1965-),,,,,,:[phone],E2mail:[e-mail][][1],,.[J].,2007,23(2):130-132.[2],,,.[J].,2007,10(4):315-317.[3],,,.[J].,2006,15(9):736-739.[4]CHENL,QINF,MAY,etal.Quantitativedeterminationofaz2ithromycininhumanplasmabyultraperformanceliquidchroma2tography2electrosprayionizationmassspectrometryanditsapplica2tioninaphar