液质联用测定健康人血浆中莫雷西嗪浓度及其药代动力学研究

Determination of moricizine concentration and its pharmacokinetics in healthy volunteers by LC/MS

目的 建立液质联用法并测定人血浆中莫雷西嗪浓度。方法 色谱条件 为Kromasil C18(150 mm×4．6mm,5μm),流动相:乙腈-10mmol·L-1醋酸铵 缓冲液-冰醋酸(50:50:0．45);质谱条件为离子源大气压化学电离源(APCI 源),定量分析离子分别为m／z 427．9(莫雷西嗪)和m／z 326．9(氯氮平)。结果 线性范围为10．0-4 000 ng·mL-1,萃取回收率在(72．74±3．61)％,日内、 日间的RSD皆<15％;用3P97计算主要药代动力学,经双因素方差分析:tmax为 (1．46±0．38)h;Cmax为(550．8±279．3)ng·mL-1;t1／2为(2．41±0．92)h;用 梯形法计算,AUC0-t和AUC0-∞分别为(1 529．4±726．7),(1 585．3±740．7)ng ·h·mL-1。结论 本方法适于测定血浆中莫雷西嗪浓度及其进行人体生物 等效性研究。

Objective To develop a LC/MS method for quantifying moraci- zine in healthy human plasma. Methods LC ： Use Kromasil C18 （ 150 mm × 4. 6 mm ,5 μm）with the mobile phase consisting of acetonitrile -10 mmol · L^-1 acetateamine buffer - glacial acetic acid （ 50 ： 50 ： 0. 45 ） . MS ： Equipped with an atmospheric pressure chemical ionization （APCI） source was used as detector and was operated in positive ion mode selected reaction monitoring （SRM） mode with the transitions of m/z 427. 9 and m/z 326.9 used as quantify moricizine and clozapine, respectively. Results the calibration curve was linear over the concentration range of 10. 00 -4 000 ng · mL ^- 1, the extracted recovery was （ 72. 74 ± 3.61 ） %. Within - day and between -day precise expressed by relative standard derivation （RSD） less than 15%. The main pharmareokinetic parameters were follows： tmax Was （1.46 ±0.38）h; Cmax was （550.8 ±279.3）ng · mL^-1; t1/2 was （2.41 ± 0.92）h, AUC0-t and AUC0-∞ were （1529.4 ±726.7 ）ng· h· mL^-1 and （1585.3 ±740. 7） ng · h· mL^-1 respectively by using trapezoid method. Conclusion The assay method is shown to be sensitive, fast, suitable and accurate for determination of moricizine in human plasma.