液相色谱-串联质谱法测定人血浆中替扎尼定

目的: 建立灵敏的液相色谱-串联质谱法测定人血浆中替扎尼定的浓度。 方法: 血浆样品碱化后经乙醚液-液萃取,以甲醇-10 mmol· L^-1醋酸铵-甲酸(55∶ 45∶ 0.1,v/v/v)为流动相,采用Zorbax SB C₁₈柱(150 mm×4.6 mm,5 μm)分离,通过电喷雾电离源,以选择反应监测(SRM)方式进行正离子检测,用于定量分析的离子反应分别为m/z 254→44(替扎尼定)和m/z 243→210(内标,石杉碱甲)。 结果: 测定血浆中替扎尼定方法的线性范围为10.0~5000 pg·mL^-1,定量下限可达10.0 pg·mL^-1。日内、日间精密度(RSD)均小于10.0%,准确度(RE)在±3.6%以内。 结论: 本方法灵敏度高,血浆用量少,适用于替扎尼定制剂的人体药物动力学研究。

Objective: To develop and validate a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of tizanidine in human plasma. Methods: Tizanidine and the internal standard huperzine A were separated from plasma by alkalinized liquid-liquid extraction with diethyl ether.Chromatographic separation was performed on a Zorbax SB C₁₈(150 mm×4.6 mm,5 μm)column with an isocratic mobile phase consisting of methanol-10 mmol·L^-1 ammonium acetate-formic acid (55∶ 45∶ 0.1,v/v/v).A tandem mass spectrometer equipped with electrospray ionization source was adopted as detector.Selected reaction monitoring (SRM) transitions of m/z 254→44 and m/z 243→210 were measured in positive mode for tizanidine and internal standard,respectively. Results: The linear concentration range of the calibration curve for tizanidine was 10.0-5000 pg·mL^-1.The lower limit of quantification was 10.0 pg·mL^-1.The intra-day and inter-day relative standard deviation over the entire concentration range was less than 10.0%.The accuracy was within 3.6% in terms of relative error. Conclusion: The method is sensitive and suitable for pharmacokinetic study of tizanidine in human subjects.