Pharmacokinetic Study Of Bicyclol In Human

Methods for the determination of bicyclol in plasma samples based on liquid chromatography-tandem mass spectrometry(LC-MS/MS)and ultra performance convergence chromatography-tandem mass spectrometry(UPC2-MS/MS)have been developed and validated.To evaluate the pharmacokinetic properties of bicyclol tablets in healthy Chinese volunteers,LC-MS/MS methods for quantifying bicyclol in human plasma were established.The concentration-time curves were drawed and the pharmacokinetic parameters were calculated based on the concentrations determined.The results provided a guidance for clinical medication.The quantitative methods,which is simple,rapid,sensitive,accurate,precise,reliable,can be applied to the clinical pharmacokinetic study of retagliptin phosphate tablets.METHODA UPC2-MS/MS methods for quantifying bicyclol in human plasma were established.Plasma samples were precipitated with acetonitrile,3 obtained 1 supernatant,entering the UPC2-HSS C18 SBcolumn(3.O×50mm,1.8um)chromatographic column by gradient elution mode were separated modifier for methanol acetonitrile,containing 0.2%formic acid and methanol as a compensating flow was 0.2ml/min and analysis time was 4.0 minutes.Electrospray ionization(ESI)source was applied and operated in the positive ion mode.Multiple reaction monitoring(MRM)mode were used to quantify bicyclolthe quantification of the ion,respectively:m/z408.10?314.03,and m/z419.12?386.98.In this study,a highly sensitive and rapid method based on liquid chromatography-tandem mass spectrometry(LC-MS/MS)for the simultaneous quantitation of bicyclol in bio-matrix has been developed and validated according to CFDA guidelines.Mass spectrometry detection was performed on a QTRAP 2000 mass spectrometerequipped with an ESI source operated in the positive ionization mode.Under Q1 full scan mode,strong signals ofprotonated molecular[M+NH4]+ ions of bicyclol and IS were found.Different CE values were tested to produce the most abundant and stableproduct ions.As a result,the ion transitions of m/z408.10?314.03,m/z419.12?386.98 were therefore selectedfor MRM of bicyclol and IS,respectively.Agilent ZorboxSB C18(4.6×150 mm I.D.,5 ?m,Agilent,USA)presented a good resolution and excellent peak shapes for analytes and ISwhen a gradient elution withacetonitrile and 2mM ammonium acetate was operated at a flow rate of 1.0 mL/min.Protein precipitation was used to purified plasma samples for thereasons of sample process.Acetonitrile at a certain volume of 660 ?L was chosen as protein precipitant due to its low solvent effect and preferable precipitationefficiency.After precipitation,the supernate was diluted by mobile phase to reduce matrixeffectbefore injected into the LC-MS/MS system.RESULTSMethods for the determination of bicyclol in plasma samples based on liquid chromatography-tandem mass spectrometry(LC-MS/MS)and ultra performance convergence chromatography-tandem mass spectrometry(UPC2-MS/MS)have been developed and validated.To evaluate the pharmacokinetic properties of bicyclol tablets in healthy Chinese volunteers,LC-MS/MS methods for quantifying bicyclol in human plasma were established.The concentration-time curves were drawed and the pharmacokinetic parameters were calculated based on the concentrations determined.The results provided a guidance for clinical medication.The quantitative methods,which is simple,rapid,sensitive,accurate,precise,reliable,can be applied to the clinical pharmacokinetic study of retagliptin phosphate tablets.The validation of method is fully progressed according with China Food and Drug Administration(CFDA)guidance.