目的 建立高效液相色譜-質(zhì)譜聯(lián)用（HPLC-MS/MS）測定大鼠血漿中美西律的血藥濃度的方法，用于ig鹽酸美西律片后大鼠體內(nèi)的藥動學(xué)研究。方法 采用Waters XBridge^TM C₁₈色譜柱（100 mm×2.1 mm，3.5 μm）；流動相：0.1%甲酸水-乙腈；梯度洗脫；體積流量為0.3 mL/min；柱溫：30℃；進(jìn)樣量：5 μL。采用電噴霧離子源，多反應(yīng)監(jiān)測模式，正離子監(jiān)測，美西律和地西泮（內(nèi)標(biāo)）的定量離子分別為m/z 180.2→58.2、285.0→154.1。經(jīng)DAS 1.0軟件統(tǒng)計(jì)分析，得到大鼠ig鹽酸美西律片62.5 mg/kg的藥動學(xué)參數(shù)。結(jié)果 美西律在5~5 000 ng/mL線性關(guān)系良好。精密度試驗(yàn)RSD值和準(zhǔn)確度試驗(yàn)RE值分別在1.08%~8.96%和-6.00%~9.45%。提取回收率和基質(zhì)效應(yīng)分別為44.07%~64.35%和71.07%~84.52%。動力學(xué)過程符合一室模型，給藥后30 min左右達(dá)峰，半衰期大約為2 h，消除速度較快，24 h消除完全。結(jié)論 該方法高效、專屬性強(qiáng)、靈敏度高，可用于美西律藥動學(xué)的研究。

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 XBridge^TM 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.

國家自然科學(xué)基金資助項(xiàng)目面上項(xiàng)目（81673824）；國家自然科學(xué)基金資助項(xiàng)目青年科學(xué)基金項(xiàng)目（81503457）