RP-HPLC法测定人血浆中拉莫三嗪及药动学

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。

RP-HPLC determination of lamotrigine in human plasma and its pharmacokinetic studies

Objective To develop a rapid and sensitive method for the determination of lamotrigine in human plasma by RP-HPLC for pharmacokinetic study. Methods Lamotrigine and internal standard were extracted from plasma with ethyl acetate and separated on a Kromasil C₁₈ column using a mobile phase of acetonitrile-20 mmol·L^-1 monopotassium phosphate (V:V=25:75) at a flow rate of 1.0 mL·min^-1. Quantitation was performed by measurement of the UV absorbance at a wavelength of 306 nm. Eleven healthy volunteers were given a single oral dose of 50 mg lamotrigine tablets, and the pharmacokinetic parameters were calculated by DAS 2.0 software using standard noncompartmental method. Results The assay was linear over the concentration range of 10.0-2000.0 µg·L^-1 for lamotrigine. The intra-day and inter-day precision was less than 8.0% and accuracy was within ±2.6%. The extraction recovery was more than 59.1%. The main pharmacokinetic parameters of lamotrigine were as follows: t_1/2 (39.1±8.2) h, t_max (3.3±1.8) h, ρ_max (469.6±152.4) µg·L^-1, AUC_0-t (2 2424.6±6 952.6) µg·h·L^-1, AUC_0-∞(2 5573.2±7 196.4) µg·h·L^-1. Conclusions The method is simple, rapid, sensitive and can be applied to human pharmacokinetic studies of lamotrigine.