高效液相色谱法同时测定人血浆中6种抗癫痫药物及两种活性代谢物的浓度

Study on Simultaneous Analysis of Six Antiepileptic Drugs and Two Active Metabolites in Human Plasma by HPLC

目的建立了同时测定人血浆中扑米酮（PRI）、拉莫三嗪（LTG）、苯巴比妥（PB）、苯妥英（PHT）、奥卡西平（OXC）、卡马西平（CBZ）压两种活性代谢物单羟奥卡西平（MHD）、环氧卡马西平（CBZE）浓度的HPLC方法。方法以盐酸普萘洛尔为内标，血浆样品经蛋白沉淀法处理后直接进样测定。色谱柱采用Agilent RX—C8柱（4．6mm×250mm，5μm），流动相为甲醇-乙腈-体积分数0．1％三氟乙酸水溶液（20：13．5：66．5）。双波长双通道检测，在215nm测定PRI，LTG，MHD，PB和CBZE，235nm测定OXC，PHT和CBZ。结果PRI，LTG，MHD，PB，CBZE，OXC，PHT和CBZ的线性范围分别是5-50，1-25，1～50，5-100，1～10，0．5～25，1—50，1—25mg·L^-1。平均方法回收率分别为98．7％，97．0％，97．9％，102．9％，100．0％。99．2％，100．1％和101．7％。各待测组分的日内、日间RSD均小于11．6％。结论本法操作简便，结果准确，适用于临床治疗药物监测。

OBJECTIVE To establish a simple HPLC method for the simultaneous determination of pfimidone （PRI）, lamotrigen （LTG）, phenobarbital （PB）, phenytoin（PHT）, oxcarbazepine （OXC）, carbamazepine（CBZ） and two active metabolites of monohydroxycar bazepine （MHD）, carbamazepine 10,11-epoxide（CBZE） in human plasma.METHODS The analytes were extracted by protein precipitation, using propranolol hydrochlofide as internal standard. The extracts were injected onto an Agilent RX-C8 column, and the mobile phase consisted of methanol-acetonitril-0.1% triflouroacetic acid （20：13.5：66.5）. PRI, LTG, MHD, PB and C BZE were detected at the wavelength of 215 nm, while OXC, PHT and CBZ were detected at 235 nm. RESULTS The method was found to be linear over the concentration ranges inves- tigated, 5 - 50 mg·L^-1 for PRI, 1 - 25 mg·L^-1 for LTG, 1 - 50 mg·L^-1 for MHD, 5 - 100 mg·L^-1 for PB, 1 - 10 mg·L^-1for CBZE, 0.5 - 25 mg·L^-1 for OXC, 1- 50 mg·L^-1 for PHT and 1 - 25 mg·L^-1 for CBZ. The recoveries of PRI, LTG, MHD, PB, CBZE, OXC, PHT and CBZ were 98.7%, 97.0%, 97.9%, 102.9%, 100.0%, 99.2%, 100.1% and 101.7%, respectively. The intra-and inter-day validation were adequate with the RSDs of 11.6% or below. CONCLUSION This method is proved to be convenient, accurate and suitable to measure concentrations of the eight analytes in clinical samples.