高效液相色谱法测定丙戊酸钠的血药浓度

HPLC Method for Determination of Sodium Valproate Serum Concentration

目的建立测定血清中丙戊酸(VPA)血药浓度的高效液相色谱法。方法血清用正己烷提取,α-溴苯乙酮为衍生试剂,环己烷羧酸为内标,采用Zorbbx SB C18柱(250 mm×4.6 mm,5μm)为分析柱;流动相为甲醇-水(79∶21,V/V),检测波长为248 nm,流速为1.0 mL/min,设计个体化给药方案。结果内标环己烷羧酸和丙戊酸的保留时间分别为6.3 min和9.3 min,质量浓度线性范围为12.5～200μg/mL(r=0.999 9),平均回收率为99.98%,日内、日间RSD均小于5.66%。结论该法快速、简单、准确性好,适用于临床进行丙戊酸的血药浓度监测。

Objective To establish the HPLC method for the serum concentration determination of valproic acid（VPA）and to guide the individualized medication regimen by analying the typical cases. Methods Serum was extracted with hexane. With α- bromoacetophenone as the derivative reagent and cyclohexane carboxylic acid as the internal standard,the Zorbbx SB-C18 column（250 mm ×4.6 mm,5 μm） was adopted as the analytical column;the mobile phase was methanol-water（79：21, V/V）,the detection wave length was set at 248 nm, the flow rate was 1.0 mL/min. The above mentioned method was used to determine the dozens of cases using sodium valproate. From them, 3 typical cases were selected for discussing the influencing factors of the serum sodium valproate concentration and designing the individualized drug administration regimen. Results The retention time of internal standard cyclohexane carboxy acid and VPA was 6.3 min and 9.3 min respectively,the linear range was 12.5-200 ~g/mL,the ratio of the sodium valproate peak height and the internal stan- dard peak height showed good linear relation with the concentration（r =0. 999 9）. The average recovery rate was 99.98%, RSD of in- tra- day and inter-day was less than 5.66%. At the same time,during the process of the practical measurement of serum drug con- centrations,it was founded that the same dosage of sodium valproate could produce a larger gap of the blood drug concentration in dif- ferent individuals. Conclusion This method is rapid, simple, accurate and suitable for serum sodium valproate concentration monitor- ing. In order to adjust the individualized dosing regimen,the serum sodium valproate concentration monitoring is necessary.