HPLC测定人血浆中吡仑帕奈的浓度及其儿科临床应用

Determination of Perampanel Concentration in Human Plasma by HPLC and Its Clinical Application in Pediatrics

关键词:  吡仑帕奈  高效液相色谱法  血药浓度  临床应用

Key words:  perampanel  HPLC  plasma concentration  clinical application

摘要:

目的 建立HPLC测定人血浆中吡仑帕奈浓度的方法并考察其临床应用。方法 采用Agilent ZORBAX SB-C₁₈(4.6 mm×150 mm，5 μm)色谱柱，流动相为0.05%磷酸(pH 3.5)-乙腈(56∶44)，流速为1 mL·min^–1，柱温为30℃，检测波长为290 nm。测定癫痫患儿的吡仑帕奈浓度并考察影响血药浓度的风险因素。结果 吡仑帕奈在75~2 500 μg·L^–1内线性良好，定量限为75 μg·L^–1，准确度不超过标示值的±10%，精密度的变异系数均≤5%，回收率为97.6%~101.0%，在实验涉及的各种条件下稳定性良好。利用该方法测定了51例癫痫患儿的吡仑帕奈血浆谷浓度，所得浓度结果为91.6~1 681.9 μg·L^–1；年龄影响吡仑帕奈浓度，<5岁患者的吡仑帕奈谷浓度显著低于5~12岁患者，但与≥12岁患者无显著差异。结论 该方法操作简便，具有较高的准确性和灵敏度，能满足吡仑帕奈治疗药物监测的分析要求，年龄对吡仑帕奈的谷浓度存在显著影响。

Abstract:

OBJECTIVE To establish an HPLC method for the determination of perampanel concentration in human plasma.METHODS The plasma samples were separated on an Agilent ZORBAX SB-C₁₈(4.6 mm×150 mm, 5 μm) column using a mobile phase of 0.05% orthophosphoric acid(pH 3.5)-acetonitrile(56:44) at a flow rate of 1 mL·min^-1. The column temperature was 30℃, and detection wavelength was 290 nm. Perampanel concentration in children with epilepsy and investigation of risk factors affecting blood concentration was determined. RESULTS The linear range of perampanel was 75-2 500 μg·L^-1, and the limit of quantitation was 75 μg·L^-1. The accuracy didn't exceed ±10% of the marked value, the precision was less than 5%, and the recovery was 97.6%-101.0%. The samples were stable at the different conditions detected. A total 51 plasma samples of children diagnosed with epilepsy were measured by the established method, and the trough concentrations of perampanel were 91.6-1 681.9 μg·L^-1. Age influenced the perampanel concentrations, the concentrations of patients younger than 5 years old was significantly lower than that aged 5-12 years, but no significant difference was found when compared with that aged older than 12 years and younger than 5 years. CONCLUSION The method is simple, accurate, sensitive and can be used for the therapeutic drug monitoring of perampanel in clinic. The age of patients has a significant impact on the trough concentrations of perampanel.