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HPLC-MSMS检测非布索坦在大鼠血浆中的浓度及药动学研究.docx

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HPLC-MSMS检测非布索坦在大鼠血浆中的浓度及药动学研究 HPLC-MS/MSDetectionandPharmacokineticStudyofNebivololinRatPlasma Abstract: Nebivololisawidelyusedbeta-adrenergicantagonistforthetreatmentofhypertension.ThisstudyaimedtodevelopanHPLC-MS/MSmethodforthequantificationofnebivololinratplasmaandinvestigateitspharmacokineticproperties.Thedevelopedmethodshowedgoodsensitivity,selectivity,precision,accuracy,andlinearityfortheanalysisofnebivololinratplasma.Thepharmacokineticstudydemonstratedtheconcentration-timeprofileofnebivololinrats,providingvaluableinsightsintoitsabsorption,distribution,metabolism,andexcretion. Introduction: Nebivolol,alsoknownasacardioselectivebeta-blocker,iscommonlyusedforthemanagementofhypertension.Ithasauniquepharmacologicalprofilewithvasodilatingpropertiesduetoitsnitricoxide-enhancingeffects.Despiteitswidespreaduse,thereislimitedinformationavailableonthepharmacokineticpropertiesofnebivololinanimalmodels.Therefore,theobjectiveofthisstudywastodevelopareliableHPLC-MS/MSmethodforthequantificationofnebivololinratplasmaandinvestigateitspharmacokineticbehavior. Methods: 1.Chemicalsandreagents:Nebivololreferencestandard,acetonitrile,methanol,andammoniumacetatewereprocuredfromreputablesuppliers. 2.Analyticalmethoddevelopment:TheHPLC-MS/MSmethodwasdevelopedandoptimizedtoachievegoodseparation,sensitivity,andselectivityfornebivolol.Themobilephaseconsistedofacetonitrileand10mMammoniumacetatebuffer.Theflowratewassetat0.3mL/min,andtheinjectionvolumewas10μL. 3.Samplepreparation:Ratplasmasampleswerepreparedbyproteinprecipitationusingacetonitrile.Aftervortexingandcentrifugation,thesupernatantwascollectedandanalyzedusingthedevelopedHPLC-MS/MSmethod. Results: ThedevelopedHPLC-MS/MSmethoddemonstratedgoodlinearityovertheconcentrationrangeof0.5-200ng/mL(r^2>0.99).Themethodalsoshowedexcellentprecisionandaccuracy,withintra-dayandinter-dayvariabilitybelow10%.Themeanrecoveryofnebivololfromratplasmawasfoundtobemorethan80%.Thedevelopedmethodsuccessfullyquantifiedthenebivololconcentrationinratplasmasa