RP-HPLC法测定人血清中丙戊酸浓度及在癫痫患儿中的应用

目的：建立测定人血清中丙戊酸浓度的方法及其在癫痫患儿中的应用。方法：血清样品处理后采用反相高效液相色谱法测定,色谱柱为Diamonsil C18,流动相为甲醇-水（77∶23）,柱温为30℃,流速为1.0ml/min,检测波长为248nm,内标为环己烷羧酸;对97例癫痫患儿进行丙戊酸血药浓度的测定。结果：丙戊酸最低检测浓度为19.43mg/L;血药浓度在19.43～275.86mg/L范围内线性关系良好（r=0.9998）;平均相对回收率为101.88%～105.90%;日内RSD为2.96%～7.71%,日间RSD为5.22%～9.26%。97例/次癫痫患儿丙戊酸血药浓度在治疗范围（50～100mg/L）内的有54例/次,占55.7%;低于有效治疗范围（〈50mg/L）的有33例次,占34.0%;高于有效治疗范围（〉100mg/L）有10例/次,占10.3%。结论：本方法灵敏、准确、快捷,可用于癫痫患儿丙戊酸临床血药浓度监测。

Determinination of the Concentration of Valproate Acid in Human Serum by RP-HPLC and Its Applica- tion in Epileptic Children

OBJECTIVE： To establish a method for determining the concentration of valproate acid in human serum and its ap plication in epileptic children. METHODS： RP-HPLC was adopted after serum sample was treated. A Diamonsil C8 colunm was used with mobile phase consisted of methanol-water （77：23） at the flow rate of 1.0 ml/min. The detection wavelength was set at 248 rim, and column temperature was 30 ℃. The cyclohexanecarboxylic acid was used as internal standard. The serum concentrations of valproate acid in 97 epileptic children were monitored. RESULTS： The minimal detectable concentration of valproate acid was 19.43 mg/L. The linear range of valproate acid was 19.43-275.86 mg/L （r=0.999 8） with average recoveries of 101.88%-105.90%. The RSDs of inter-day and intra-day were 2.96%-7.71% and 5.22%-9.26%. In 97 children, there were 33 cas- es whose serum concentration of valproate acid were below 50 mg/L （34.0%） , 54 cases were in the range of 50-100 mg/L （55.7%）, and 10 cases were over 100 mg/L （10.3%）. CONCLUSIONS： The method is sensitive, accurate and rapid for clinical pharmacokinetic monitoring of valproate acid in epileptic children.