LC-MS/MS法测定人血浆中替利定和去甲替利定的质量浓度

目的: 建立LC-MS/MS法测定人血浆中替利定和去甲替利定的质量浓度。 方法: 选用Agilent-Zorbax-Eclipse-XDB-C₁₈色谱柱,以甲醇-1 mmol·L^-1醋酸铵(75∶25)为流动相,采用正离子,多反应监测方式测定样品质量浓度。用于定量分析的离子对分别为[M+H]⁺ m/z 274.3→m/z 155.1(替利定) ,[M+H]⁺m/z 260.2→m/z 155.1 (去甲替利定)和[M+H]⁺m/z 284.8→m/z 192.9 (地西泮)。 结果: 血浆样品中,替利定在0.5~250 ng·mL^-1范围内线性关系良好(r=0.9936),最低定量质量浓度为 0.5 ng·mL^-1;去甲替利定在1~500 ng·mL^-1范围线性关系良好(r=0.9948),最低定量质量浓度为1 ng·mL^-1。二者日内与日间 RSD 均小于 15%,平均回收率高,且稳定性均较好。 结论: 本方法简便快速、灵敏准确、特异性强,适用于盐酸替利定和去甲替利定的体内药代动力学研究。

Objective: To establish a high performance liquid chromatography-mass spectrometry method for the determination of tilidine and nortilidine in human plasma. Methods: The sample were separated on an Agilent-Zorbax-Eclipse-XDB-C₁₈ column with methanol-1 mmol·L^-1 ammonium acetate(75∶25)as the mobile phase with the multiple reaction monitoring in the positive ion mode.The transitions of [M+H]⁺ m/z 274.3→m/z 155.1 (tilidine),[M+H]⁺m/z 260.2→m/z 155.1 (nortilidine) and [M+H]⁺m/z 284.8→m/z 192.9 (diazepam) were used to quantify them,respectively. Results: In plasma,the calibration curve for tilidine was linear over the concentration range of 0.5-250 ng·mL^-1(r=0.9936),the minimum detectable concentration was 0.5 ng·mL^-1;The calibration curve for nortilidine was linear over the concentration range of 1-500 ng·mL^-1 (r =0.9948),the minimum detectable concentration was 1 ng·mL^-1.The inter- and intra-day precisions(RSDs) were both less than 15%,the average recovery was high,and stabilities were good. Conclusion: The method is simple,rapid,sensitive and accurate on their pharmacokinetic study of tilidine and nortilidine in the human body.

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