超高效液相串联质谱法测定大鼠血浆中(S)-MP 3950的浓度及其药代动力学研究

Determination of( S )-MP 3950 in rat plasma by ultra performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study

目的建立超高效液相串联质谱(UPLC-MS/MS)法测定新型胃动力候选药(S)-MP 3950在大鼠血浆中的浓度并应用于药代动力学研究。方法血浆样品用乙酸乙酯提取,色谱柱为ACQUITY UPLC~BEH C18柱(2.1 mm×50 mm,1.7μm);流动相为甲醇-5 mmol·L^(-1)醋酸铵(含体积分数为0.1%的甲酸)(55∶45),流速为0.2 mL·min^(-1),柱温30℃;质谱检测用电喷雾离子(ESI)源,正离子模式下采用多反应监测(MRM)模式,分析时间为3.0 min。用DAS 2.0软件以非房室模型计算药代动力学参数。结果 (S)-MP 3950在大鼠血浆中的线性范围为10~5000μg·L^(-1)。定量下限为10μg·L^(-1)。日内、日间精密度(RSD)均不大于7.9%,准确度(RE)为0.1%~8.5%。结论此方法快速、灵敏,准确,成功应用于大鼠血浆中(S)-MP 3950浓度的测定及其药代动力学研究。

Objective To develop an ultra performance liquid chromatography- tandem mass spectrometry（ UPLC- MS / MS） method for the study of pharmacokinetics of（ S）- MP 3950,a novel gastroprokinetic agent candidate in rats. Methods The plasma samples were extracted by liquid- liquid extraction（ LLE） with ethyl acetate. An ACQUITY UPLC~BEH C（18）column（ 2. 1 mm × 50 mm,1. 7 μm） was used with a mobile phase consisting methanol and 5 mmol · L^-1ammonium acetate with 0. 1% formic acid（ v ∶ v = 45 ∶ 55）. The analysis was performed in multiple reaction monitoring（ MRM） mode via positive electrospray ionization source on a triple quadrupole tandem mass spectrometer. The whole analysis time was 3. 0 min. The pharmacokinetic parameters were calculated by DAS 2. 0 program. Results The method had a lower limit of quantification（ LLOQ） of 10 μg·L^-1,linear up to 5000 μg·L^-1.The intra- and inter- day precision（ relative standard deviation,RSD）were all less than 7. 9%. The accuracy（ relative error,RE） was from0. 1% to 8. 5%. Conclusion The method was proved to be rapid,sensitive and accurate for pharmacokinetic study of（ S）- MP 3950 in rats.