丙戊酸钠血药浓度测定衍生因素分析

Analysis the influencing factors on plasma concentration of valproic acid sodium

目的:分析丙戊酸钠血药浓度测定衍生时的影响因素,保证临床测定的准确性。方法:丙戊酸钠血药浓度用高效液相色谱(HPLC)法测定。血浆样品用2-溴-对硝基苯乙酮为衍生试剂,以丙戊酸钠衍生物产率为指标,用单因素考察法考察衍生试剂浓度、三乙胺体积分数、反应温度、反应时间对丙戊酸钠衍生产率的影响。结果:衍生试剂2-溴-对硝基苯乙酮浓度为1.5~2.0mg·mL^(-1),催化剂三乙胺体积分数为20%,衍生温度和衍生时间分别为60℃,10 min时,丙戊酸衍生完全,血药浓度在10~200μg·mL^(-1)范围内,线性较好(R^2=0.999 5),回收率为95.00%~100.59%,日内与日间RSD≤5%,符合《中国药典》中对生物样本药物浓度检测的规定。结论:影响丙戊酸血药浓度测定的因素较多,如衍生试剂浓度和三乙胺体积分数、衍生时间、衍生温度等。在日常血药浓度监测过程中,我们应注意这些差异,尽量将误差控制在允许范围之内,保证丙戊酸钠治疗药物监测结果的准确性。

OBJECTIVE To analyze the influencing factors for determining plasma concentration of sodium valproate,ensure accuracy and reliability of the clinical measurement.METHODS HPLC method was adopted after samples were derivatized with2-bromo-4-nitroacetophenoe.Influence of reagent and triethylamine concentrations,reaction temperature and time on valproic acid were investigated by single factor method with the yield of the propylene acid derivatives as the parameter.RESULTS Valproic acid was fully derived when the concentration of 2-bromo-4-nitroacetophenoe was 1.5-2.0mg·mL^（-1）,the concentration of triethylamine was 20%,the reaction temperature and time were 60℃and 10 min.The linear range of sodium valproate was10-200μg·mL^（-1）（R^2=0.999 5）.The recovery was 95.0%-100.6%,and the RSD of intra-day and inter-day were less than5%（n=5）.CONCLUSION There were many factors influencing the plasma concentration of sodium valproate,such as the concentration of derivatization reagent and the concentration of triethylamine,the reaction time and temperature.In addition to the factors of error derivatized,laboratory personnel,seasonal temperature,solution storage,etc.can affect the determination of plasma concentrations.Therefore,in daily blood concentration monitoring process,these differences should be noted and controlled to a smaller level,to ensure accuracy and reliability of the drug monitoring data.