高效液相色谱法同时测定人血浆中卡马西平、奥卡西平及其活性代谢产物的浓度和临床应用

目的：建立同时测定人血浆中卡马西平（CBZ）、10，11-环氧卡马西平（CBZE）、奥卡西平（OXC）和单羟基卡马西平（MHD）浓度的高效液相色谱法，并将其应用于临床中卡马西平、奥卡西平及其活性代谢产物血药浓度的测定。方法：以苯巴比妥为内标，血浆经乙醚-二氯甲烷（2∶1）提取。色谱柱为WondaSil C₁₈柱（150 mm×4.6 mm，5 μm），流动相为甲醇∶水=50∶50，柱温30℃，流速1.0 mL·min^-1，检测波长215 nm，进样量20 μL。结果：卡马西平、10，11－环氧卡马西平、奥卡西平和单羟基卡马西平标准曲线范围分别为0.1~20，0.05~10，0.05~20，0.2~50 mg·L^-1，最低检测限分别为0.1，0.05，0.05，0.2 mg·L^-1，日内、日间精密度均小于10%。结论：该方法灵敏准确，简便快速，适用于卡马西平、奥卡西平及其代谢产物血药浓度检测。

Determination of carbamazepine,oxcarbazepine and their active metabolites in human plasma by HPLC and clinic application

OBJECTIVE To establish a HPLC method for the simultaneous determination of carbamazepine,carbamazepine-10,11-epoxide,oxcarbazepine and monohydroxy carbazepine in human plasma,and its application in clinic therapeutic drug monitoring.METHODS Phenobarbitol was used as internal standard.The plasma samples were extracted by diethylether-dichloromethane (2:1).The analyses were conducted on a WondaSil C₁₈ column (150 mm×4.6 mm,5 μm) with a mobile phase composed of methanol:water (50:50) at the flow rate of 1.0 mL·min^-1.The detection wavelength was 215 nm,and the column temperature was 30℃.RESULTS The calibration curves were linear within the range of 0.1-20 mg·L^-1 for CBZ,0.05-10 mg·L^-1 for CBZE,0.05-20 mg·L^-1 for OXC and 0.2-50 mg·L^-1 for MHD,the limits of detection were 0.1,0.05,0.05,0.2 mg·L^-1.The RSDs of inter-day and intra-day were both less than 10%.CONCLUSION The method is found to be accurate,sensitive,simple and rapid.It is suitable for the clinical study of carbamazepine and oxcarbazepine pharmacokinetics,and for drug monitoring.