RP-HPLC法同时测定4种抗癫痫药物血清浓度研究

Study on the simultaneous determination of serum concentration of four antiepileptic drugs by RP-HPLC

目的建立反相高效液相色谱(RP-HPLC)法,同时测定拉莫三嗪(LTG)、奥卡西平(MHD)、苯妥英钠(PHT)和卡马西平(CBZ)4种抗癫痫药物的血清浓度。方法选用纯甲醇为萃取溶剂,以Waters sunfine C 18柱为分离色谱柱,甲醇-水(40∶60)为流动相,流速1.0 mL/min,柱温35℃,检测波长235 nm。结果LTG、MHD、PHT和CBZ分离良好,线性范围分别为0.8~31.0、1.39~47.94、1.19~38.34、0.99~31.01μg/mL;血清最低检测浓度分别为0.02、0.27、0.47、0.05μg/mL;总平均回收率分别为99.97%、100.81%、99.74%、99.59%;日内精密度均小于3.00%,日间精密度均小于5.00%。结论RP-HPLC法稳定性好,经济简便,适用于临床联合使用抗癫痫药物的血药浓度监测。

Objective To establish a reversed-phase high-performance liquid chromatography(RP-HPLC)method for the serum concentration determination of lamotrigine(LTG),oxcarbazepine(MHD),phenytoin(PHT),and carbamazepine(CBZ).Methods Pure methanol was used as the extraction solvent.Waters sunfine C 18 column was used as the separation column.Methanol-water(40∶60)was used as the mobile phase.The flow rate was 1.0 mL/min,the column temperature was 35℃,and the detection wavelength was 235 nm.Results LTG,MHD,PHT and CBZ were well separated,with linear ranges of 0.8-31.0,1.39-47.94,1.19-38.34,0.99-31.01μg/mL respectively,and the minimum serum concentrations were 0.02,0.27,0.47,0.05μg/mL respectively.The total average recoveries were 99.97%,100.81%,99.74%and 99.59%respectively;the intra-day precision was less than 3.00%,and the inter-day precision was less than 5.00%.Conclusion RP-HPLC method has good stability,economy and simplicity.It is suitable for monitoring the serum concentration of antiepileptic drugs in clinical use.