lcmsms同时检测鸡体内3中mals残留及药动学分析-simultaneous determination of malas residues in chicken by lcm sms and pharmacokinetic analysis.docxVIP

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lcmsms同时检测鸡体内3中mals残留及药动学分析-simultaneous determination of malas residues in chicken by lcm sms and pharmacokinetic analysis.docx

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lcmsms同时检测鸡体内3中mals残留及药动学分析-simultaneous determination of malas residues in chicken by lcm sms and pharmacokinetic analysis

AbstractThemacrolideantibiotics(MALs)havesalientantibacterialactivityformycoplasmaandG+bacteria,tylosin(TYL)andtilmicosin(TILM)arefrequentlyusedinveterinaryclinicasthespecialanimalantibiotics.Theconcentrationofazithromycin(AZI)indiseasesiteissignificantlyhigherthanthatofnormalpart,itisillegallyusedinveterinaryclinicalbecauseofitsremarkableantibacterialeffect.Inappropriateuseofsuchdrugscancauseveterinarydrugresidue,whichwillposeaserioushazardtohumanhealth,soitisnecessarytomonitortheresidue.Ahighperformanceliquidchromatographytandemmassspectrometry(HPLC-MS/MS)forthedeterminationofthereMALs(TYL,TILM,AZI)wasestablishedinchicken,liver,kidneyandplasma.AndthePharmacokineticsof3MALsinchickenswasstudied.Sampleswereextractedwithacetonitrileandcleaned-upbyMCXcartridge(Plasmasamplesexcepted).ThethreeantibioticswereseparatedwithlunaC8columnbyagradientelutionprogramwith0.1%formicacid-acetonitrileand0.1%formicacid-waterasthemobilephase.Theidentificationofthreedrugswascarriedoutbypositiveelectrosprayionization(ESI+)inmultiplereactionmonitoring(MRM)mode.TheplasmaandtissuessampleswerecollectedindifferentintervalsafteroraladministrationofMALs,thendetectedbyLC-MS/MSmethod.Theconcentration-timedataof3drugsinplasmaandtissueswereanalyzedwith3P97pharmacokineticssoftware.Theresultsshowedthat:thecalibrationcurveshadgoodlinearityfor3antibioticsintherangeof1-100ng/mL,withcorrelationcoefficientgreaterthan0.998.Thelimitsofdetection(LOD)were0.3-1.0、0.1-0.6、0.3-0.7μg/kg(ng/mL)andthelimitsofquantification(LOQ)were1.0-3.0、0.3-1.5、1.0-3.0μg/kg(ng/mL)forAZI、TYL、TILMinfourmatrices.Theaveragerecoveriesvariedfrom83.5%-108.0%andtheRSDSwereintherangeof4.3%-15.2%.Theresultsindicatedtheplasmadrugconcentration-timedatasweretwo-compartmentmodelwithabsorption.Theabsorptionhalf-life(t1/2ka)ofTYLwas0.041h,theeliminationhalf-life(t1/2β)was16.03h.Thetime-pointofmaximumplasmaconcentration(Tp)andthemaximumplasmaconcentration(Cmax)were0.30hand131.27ng/mL.Theareaundertheconcentration-timecurve(AUC)was1588.62(ng/mL)·h;T