In the present study, we developed a simple, sensitive, precise, and accurate liquid chromatography-tandem mass spectrometric(LC-MS/MS) method and validated such approach for simultaneous determination of flupirtine a...In the present study, we developed a simple, sensitive, precise, and accurate liquid chromatography-tandem mass spectrometric(LC-MS/MS) method and validated such approach for simultaneous determination of flupirtine and its active metabolite D-13223 in human plasma. The flupirtine, D-13223, and stable isotope internal standard(IS) were extracted from plasma samples by liquid-liquid extraction and chromatographed on a C18 column with a mobile phase consisting of acetonitrile–water–ammonia(55:45:0.1, v/v/v) at a flow rate of 0.25 m L/min. Detection was performed on a triple quadrupole tandem mass spectrometer with an electrospray ionization source(ESI) by multiple reaction monitoring(MRM) in positive ion mode. The linear calibration curves were obtained within the concentration range of 10.00–2000.00 ng/m L for flupirtine and 2.00–400.00 ng/m L for D-13223. The intra-and inter-run RSD, calculated from quality control(QC) samples, was less than 9.26% for flupirtine and D-13223. The accuracy was –5.80%–3.31% for flupirtine and D-13223. The extraction recoveries of flupirtine, D-13223, and their IS were all between 88.3%–97.2%. The method was successfully applied to investigate the pharmacokinetic profiles of flupirtine and its active metabolite D-13223 in human plasma following peroral administration of 100 mg flupirtine maleate capsules in healthy male Chinese volunteers.展开更多
文摘In the present study, we developed a simple, sensitive, precise, and accurate liquid chromatography-tandem mass spectrometric(LC-MS/MS) method and validated such approach for simultaneous determination of flupirtine and its active metabolite D-13223 in human plasma. The flupirtine, D-13223, and stable isotope internal standard(IS) were extracted from plasma samples by liquid-liquid extraction and chromatographed on a C18 column with a mobile phase consisting of acetonitrile–water–ammonia(55:45:0.1, v/v/v) at a flow rate of 0.25 m L/min. Detection was performed on a triple quadrupole tandem mass spectrometer with an electrospray ionization source(ESI) by multiple reaction monitoring(MRM) in positive ion mode. The linear calibration curves were obtained within the concentration range of 10.00–2000.00 ng/m L for flupirtine and 2.00–400.00 ng/m L for D-13223. The intra-and inter-run RSD, calculated from quality control(QC) samples, was less than 9.26% for flupirtine and D-13223. The accuracy was –5.80%–3.31% for flupirtine and D-13223. The extraction recoveries of flupirtine, D-13223, and their IS were all between 88.3%–97.2%. The method was successfully applied to investigate the pharmacokinetic profiles of flupirtine and its active metabolite D-13223 in human plasma following peroral administration of 100 mg flupirtine maleate capsules in healthy male Chinese volunteers.
