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目的建立RP-HPLC法测定人血浆中的拉莫三嗪,并将此方法应用于拉莫三嗪片在健康受试者体内的药动学研究。方法血浆样品经乙酸乙酯提取后,采用Kromasil C18柱分离,流动相为乙腈-20 mmol.L-1 KH2PO4(体积比为25∶75),流速为1.0 mL.min-1,检测波长为306 nm。测定了11名健康受试者口服拉莫三嗪片50 mg后不同时刻血浆中拉莫三嗪的浓度,采用DAS 2.0软件以非房室模型计算药动学参数。结果拉莫三嗪的线性范围为10.0～2 000.0μg.L-1;日内和日间精密度均小于8.0%,准确度(relative error,RE)在±2.6%以内,提取回收率大于59.1%。拉莫三嗪的主要药动学参数:t1/2为(39.1±8.2)h,tmax为(3.3±1.8)h,ρmax为(469.6±152.4)μg.L-1,AUC0-t为(22 424.6±6 952.6)μg.h.L-1,AUC0-∞为(25 573.2±7 196.4)μg.h.L-1。结论该方法适用于拉莫三嗪人体药动学研究。
OBJECTIVE To establish a RP-HPLC method for the determination of lamotrigine in human plasma and to apply this method to the pharmacokinetics of lamotrigine in healthy subjects. Methods The plasma samples were extracted with ethyl acetate and separated on a Kromasil C18 column. The mobile phase was acetonitrile-20 mmol.L-1 KH2PO4 (volume ratio was 25:75), the flow rate was 1.0 mL.min-1, the detection wavelength was 306 nm. The plasma concentrations of lamotrigine in 11 healthy subjects after oral administration of 50 mg of lamotrigine tablets were measured and the pharmacokinetic parameters were calculated using DAS 2.0 software in a non-compartmental model. Results The linear range of lamotrigine was 10.0-2 000.0μg.L-1. The intra-and inter-day precision was less than 8.0%, the relative error (RE) was within ± 2.6% and the extraction recovery was more than 59.1% . The main pharmacokinetic parameters of lamotrigine were t1 / 2 (39.1 ± 8.2) h, tmax (3.3 ± 1.8) h, ρmax (469.6 ± 152.4) μg.L-1, and AUC0- 424.6 ± 6 952.6) μg.hL-1, and AUC0-∞ was (25 573.2 ± 7 196.4) μg.hL-1. Conclusion This method is suitable for human study of lamotrigine pharmacokinetics.