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[摘要]
目的 建立高效液相色谱-质谱联用(HPLC-MS/MS)测定大鼠血浆中美西律的血药浓度的方法,用于ig盐酸美西律片后大鼠体内的药动学研究。方法 采用Waters XBridgeTM C18色谱柱(100 mm×2.1 mm,3.5 μm);流动相:0.1%甲酸水-乙腈;梯度洗脱;体积流量为0.3 mL/min;柱温:30℃;进样量:5 μL。采用电喷雾离子源,多反应监测模式,正离子监测,美西律和地西泮(内标)的定量离子分别为m/z 180.2→58.2、285.0→154.1。经DAS 1.0软件统计分析,得到大鼠ig盐酸美西律片62.5 mg/kg的药动学参数。结果 美西律在5~5 000 ng/mL线性关系良好。精密度试验RSD值和准确度试验RE值分别在1.08%~8.96%和-6.00%~9.45%。提取回收率和基质效应分别为44.07%~64.35%和71.07%~84.52%。动力学过程符合一室模型,给药后30 min左右达峰,半衰期大约为2 h,消除速度较快,24 h消除完全。结论 该方法高效、专属性强、灵敏度高,可用于美西律药动学的研究。
[Key word]
[Abstract]
Objectives To establish an HPLC-MS/MS method for determination of mexiletine concentration in rat's plasma, and apply the method to mexiletine pharmacokineticsn rats ig administered with Mexiletine Hydrochloride Tablets. Methods Separation of analytes was carried on Waters XBridgeTM C18 column (100 mm×2.1 mm, 2.5 μm). The mobile phase was consisted of water (0.1% formic acid) and acetonitrile with gradient elution at a flow rate of 0.3 mL/min, and the temperature was 30℃ with injection volume of 5 μL. Electrospray ionization (ESI) source and multiple reactions monitoring (MRM) were applied to measure targeted compound in positive ion mode. The quantitative ions of mexiletine and diazepam (IS) were m/z 180.2→58.2 and 285.0→154.1, respectively. The pharmacokinetic parameters of mexiletine in rats ig administered with Mexiletine Hydrochloride Tablets (62.5 mg/kg) were obtained by the statistical analysis of DAS 1 Software. Results There were good linear relationships of mexiletine in the concentration ranges of 5-5 000 ng/mL. RSD values in precision test were within 1.08%-8.96%, and RE values in accuracy test were -6.00%-9.45%. The extraction recovery and matrix effect were 44.07%-64.35% and 71.07%-84.52%, respectively. The kinetic process conformed to a one chamber model, which reached a peak at about 30 min after administration, with a half-life of about 2 h, faster elimination and 24 h elimination. Conclusion The method has high efficiency, high specificity, and good sensitivity, and can be used to study pharmacokinetics of mexiletine.
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[基金项目]
国家自然科学基金资助项目面上项目(81673824);国家自然科学基金资助项目青年科学基金项目(81503457)