LC-MS/MS法用于他喷他多在大鼠体内的药动学研究

目的建立测定大鼠血浆中他喷他多浓度的LC-MS/MS法,用以研究他喷他多在大鼠体内的药动学行为。方法采用甲醇沉淀蛋白法提取血浆中目标成分。色谱条件:色谱柱为DiamonsilC18柱,流动相为甲醇-5 mmol.L-1醋酸铵-乙酸(体积比58∶42∶0.5),流速为0.5 mL.min-1,柱温为室温。以多反应离子监测(MRM)方式,在正离子模式下进行检测,用于定量分析的主要离子对分别为m/z 222.2→107.1(他喷他多),m/z 307.1→220.1(氟康唑)。结果血浆中内源性物质不干扰他喷他多的测定,他喷他多的线性范围为2.0～200μg.L-1,方法的准确度在96.2%～97.5%内,日内、日间精密度均小于15%。结论作者建立的LC-MS/MS法,简单快速、专属性强,可用于他喷他多在大鼠体内的药动学研究。

LC-MS/MS method for the determination of tapentadol in rats

Objective To develop a sensitive and rapid LC-MS/MS method to determine the concentration of tapentadol in rat plasma.Methods After the extraction from plasma by protein precipitation,analytes and internal standards were separated by a Diamonsil C18 column.Methanol-5 mmol · L-1ammonium acetate-acetic acid(V∶ V∶ V=58∶ 42∶ 0.5)were used as the mobile phase.The multiple reaction monitoring(MRM)was used for quantitative determination in positive mode.The transitions were m/z:222.2→107.1 for tapentadol(+),m/z:307.1→220.1 for fluconazol(IS,+).Results No significant interferences for the detection of tapentadol and fluconazol from endogenous substances in plasma were observed in the present study.The calibration curve was linear over the range of 2.0-200 μg · L-1 for tapentadol.The accuracy was in the range of 96.2%-97.5% and the inter-day and intra-day precision were less than 15%.Conclusions The LC-MS/MS method is simple,rapid and sensitive enough for the pharmacokinetic study of tapentadol in rats.