马来酸依那普利的高效液相色谱测定方法及其在药动学研究中的应用

A High Performance Liquid Chromatographic Method to Detect Enalapril Maleate in Human Plasma and Its Application in Clinical Pharmacokinetic Study

目的建立测定人血浆马来酸依那普利浓度的高效液相色谱方法并进行药动学研究。方法色谱柱为ZORBAX SB—C18（4．6mm×150mm，5μm），流动相为乙腈：0．1mol·L^-1磷酸二氢钠溶液（pH：3．0）：水=27：20：53（v／v／v），流速：1．0mL·min^-1，检测波长：0～5min286nm，～8min210nm，-10min286nm；10例健康志愿者口服马来酸依那普利片，计算主要药动学参数，用DAS2．0程序处理。结果马来酸依那普利的血药浓度在5～400μg·L^-1内，与其峰面积有良好的线性关系（r=0．9999），该法测得主要药动学参数为：Cmax为（283．03±37．50）μg·L^-1，tmax为（0．83±0．12）h，t1／2为（1．56±0．32）h，AUC0-1为（711．51±91．18）μg·h·L^-1，AUC0-∞为（742．68±98．06）μg·h·L^-1。结论该方法简单，专属性强，灵敏和准确，适合依那普利的药动学研究。

Objective To establish a high performance liquid chromatography method for the determination and pharmaeokinetie study of enalapril maleate in healthy human. Methods Agilent 1100 series HPLC system was appliedwith the column ZORBAX SB-CI8 （4.6 mm× 150 mm, 5 μm）. The mobile phase was composed of methanol （0.1 mol · L^-1 ） , NaH2 PO4 （pH =3.0）and water with a ratio of 27 ： 20 ： 53（V/V/V） ,and the flow rate was 1.0 mL · min^-1. The UV detection wavelength was 0 -5 min 286 nm ,5 -8 rain 210 nm and 8 - 10 rain 286 nm. After oral administration of 20 mg enalapril maleate table in 10 voluteers, concentration-time profile was simulated and pharmacokinetic parameters were calculated with DAS software. Results The calibration curve was linear in the range from 5 to 400 μg · L^-1 （ r = 0. 999 9 ） , The main pharmacokinetic parameters after a single oral dose of 20 mg of eualapril maleate tables were as follows ： Cmax = （283.03 ± 37.50） μg · L^-1 , tmax = （0. 83 ± 0. 12） h, t1/2 = （1.57 ±0.32） h,AUCo,t = （711.51 ±91.18） μg · L^-1, andAUC 0-∞ = （742.68 ±98.06） μg · L^-1. Conclusion The method was simple, sensitive, and accurate for clinical study of enalapril maleate.