高效液相色谱法测定人血浆中奥卡西平及其活性代谢产物的浓度

Determination of the concentration of oxcarbazepine and its active metabolites in human plasma by HPLC

目的建立同时测定人血浆中奥卡西平(OXC)及其活性代谢产物利卡西平(MHD)浓度的方法。方法血浆样品采用二氯甲烷处理后,以高效液相色谱法进样测定;采用Hypersil C18色谱柱(250mm×4.6 mm,5μm),流动相为乙腈-水(21∶79,v/v),流速为1.0 m L·min^(-1),二极管阵列检测器检测波长为235 nm,柱温为35℃。结果 OXC、MHD血药浓度分别在0.32~40.96(r=0.9998)和0.344~44.1(r=0.9999)μg·m L^(-1)内与峰面积线性关系良好,检测限均为0.1μg·m L^(-1);两者低、中、高浓度方法的相对回收率分别为103.0%、85.47%、97.7%和85.99%、80.07%、95.0%,绝对回收率分别为86.75%、72.81%、78.44%和73.49%、80.35%、72.87%;日内和日间精密度均<5%(n=5)。结论该方法准确、灵敏、简便、快速,可用于OXC和MHD血药浓度检测和药物代谢动力学研究。

Objective To establish a method to determine the concentration of oxcarbazepine and its active metabolites licarbazepine in human plasma. Methods Plasma samples were detected by HPLC after being processed by dichloromethane. The column was Hypersil C18 with the mobile phase of acetonitrile-water（21∶79, v/v） at 1.0 m L·min-1. The column temperature was 35 ℃, and the detection wavelength was 235 nm. Results Good linearity was found for oxcarbazepine and metabolites licarbazepine at 0.32- 40.96 μg·m L-1（r =0.9998） and 0.344- 44.1 μg·m L-1（r = 0.9999） respectively. The limit of detection was 0.1 μg·m L-1. The relative average recovery of low, middle and high concentration for oxcarbazepine and metabolites licarbazepine were 103.0%, 85.47%, 97.7% and 85.99%, 80.07%, 95.0%, respectively. The absolute average recoveries was 86.75%, 72.81%, 78.44% and 73.49%, 80.35%, 72.87%, respectively. The RSDs of intra-day and inter-day variation were less than 5%（n = 5）. Conclusion The method is accurate, sensitive, simple and quick, which can be used for clinical drug monitoring and pharmacokinetics study.