基于HPLC同时监测癫痫患者卡马西平和苯妥英钠血药浓度及合理用药分析

Simultaneous monitoring of the plasma concentration of carbamazepine and phenytoin sodium in patients with epilepsy by HPLC and analysis of rational drug use

目的建立高效液相色谱法(HPLC)同时监测癫痫患者卡马西平和苯妥英钠的血药浓度,分析血药浓度的影响因素。方法利用InertSustain-C18(250 mm×4.6 mm,5μm)色谱柱进行试验,流动相为甲醇水溶液(50∶50),流速为1.0 mL/min,紫外检测波长为240 nm。对该方法进行方法学考察。按照给药方案将我院168例癫痫患者分为三组,应用HPLC对患者血药浓度进行监测。结果此色谱条件专属性好,方法学考察均符合要求。联合用药组患者血药卡马西平及苯妥英钠浓度均低于卡马西平组和苯妥英钠组(P<0.01)。青年患者血药卡马西平浓度高于老年患者(P<0.01)。成年患者血药苯妥英钠浓度高于青年和老年患者(P<0.01),老年患者血药苯妥英钠浓度低于青年患者(P<0.05)。结论 HPLC的专属性、线性与范围、定量限、提取回收率、精密度及重复性良好,可用于临床血药浓度监测。卡马西平和苯妥英钠联合用药会降低血药浓度;年龄差异对两种药物血药浓度有明显影响。临床可根据有效血药浓度为患者制定个性化的用药方案。

Objective To establish a high performance liquid chromatography(HPLC)method to simultaneously monitor the plasma concentration of carbamazepine and phenytoin sodium in epileptic patients,and analyze the influencing factors of plasma concentration.Methods The test was performed on InertSustain-C18(250 mm×4.6 mm,5μm)column with methanol aqueous solution(50∶50)as mobile phase,flow rate of 1.0 mL/min and UV detection wave length of 240 nm.The methodology of this method was investigated.According to the administration plan,168 epileptic patients enrolled in our hospital were divided into three groups,and the plasma concentration was monitored by HPLC.Results The chromatographic conditions had good specificity,and the methodology met the requirements.The plasma concentration of carbamazepine and phenytoin sodium in the combined medication group were lower than those in the carbamazepine group and phenytoin sodium group(P<0.01).The plasma carbamazepine concentration in the young patients was higher than that in the elderly patients(P<0.01).The plasma phenytoin sodium concentration in the adult patients was higher than that in the young and the elderly patients(P<0.01),and the plasma phenytoin sodium concentration in the elderly patients was lower than that in the young patients(P<0.05).Conclusion HPLC has good specificity,linearity and range,limit of quantitation,extraction recovery,precision and repeatability,and can be used for clinical monitoring of plasma concentration.The combination of carbamazepine and phenytoin sodium can reduce the plasma concentration of patients.Age difference has a significant effect on the plasma concentration of the two drugs.Individualized medication plan can be made for patients according to the effective plasma concentration.