RP-HPLC法同时测定卡马西平、拉莫三嗪、苯巴比妥、苯妥英钠及环氧卡马西平的血清浓度

目的: 建立同时测定血清中卡马西平(CBZ)、拉莫三嗪(LTG)、苯巴比妥(PB)、苯妥英钠(PHT)及10,11-环氧卡马西平(CBZE)血清浓度的反相高效液相色谱法。方法: 0.1ml样本血清经1ml二氯甲烷∶异丙醇(95∶5)混合溶液提取,以氟西泮(FZP)为内标,流动相为乙腈:磷酸盐缓冲液(30∶70),37℃下经SymmetryRP18(150mm×3.9mm,5μm)色谱柱洗脱、分离,220nm紫外波长检测。结果: 在一定浓度范围内(CBZ:0.47~30.00mg·L^-1,LTG:0.63~40.00mg·L^-1,PB:1.25~80.00mg·L^-1,PHT:0.63~40.00mg·L^-1,CBZE:0.31~20.00mg·L^-1)各被测药物与内标的峰面积之比与浓度呈良好的线性关系,回收率均高于95%(95%~104%,n=6),日内和日间变异均小于4%(0.76%~3.97%,1.34%~3.76%,n=6)。结论: 本方法操作简便,精密度好,回收率高,经临床用于常用抗癫痫药血药浓度的监测,其结果稳定可靠,可为临床进行群体药动学研究及实施个体化给药提供真实可信的资料。

Simultaneous determination of carbamazepine,lamotrigine, phenobarbital,phenytoin and 10, 11-carbamazepine epoxide in serum by reversedphase high performance liquid chromatography

AIM: To develop a simple and sensitive method for the simultaneous determination of carbamazepine (CBZ), lamotrigine (LTG), phenobarbital (PB), phenytoin (PHT) and 10, 11-carbamazepine epoxide (CBZE)in human plasma by reversed-phase high performance liquid chromatography (RP-HPLC).METHODS: 0.1 ml serum was extracted from dichloromethane:isopropanol (95 ∶5).Flurazepam(FZP)was adopted as internal standard.The mobile phase was composed of acetonitrile-potassium phosphate buffer (30 ∶70).The ultraviolet detector was set at 220 nm and the analysis through Symmetry RP18 stainless steel column was taken at 37 ℃.RESULTS: Peak area ratios of every drug vs.internal standard were fit to a least squares linear regression algorithm with a 1 (concentration)2 weighting in the concentration range of each drug (CBZ:0.47-30.00 mg·L^-1, LTG:0.63-40.00 mg·L^-1, PB:1.25-80.00 mg·L^-1, PHT:0.63-40.00 mg·L^-1, CBZE:0.31-20.00 mg·L^-1).The recoveries were more than 95% (95%-104%, n =6).The relative standard deviations of within-day and between-day were less than 4% (0.76%-3.97%, 1.34%-3.76%, n =6).CONCLUSION: The method is sensitive, accurate, rapid and simple.It is suitable for the clinical monitoring on most antiepileptic drugs and can provide veridical and credible data for the study of population pharmacokinetics and for the implement of individual regimen.