Abstract

Due to the difficulties in plasma concentration measurement of lisinopril, it is of utmost importance to develop a new accurate analysis method for this drug. A randomized, double-blind, two-period, two-group crossover design was conducted to scrutinize the bioequivalence of a lisinopril generic product. After administration of test or reference products to each volunteer, the active ingredient was determined in plasma samples using a developed and validated HPLC-UV method, and pharmacokinetic parameters, including C-max, T-max, AUC(0) (t), AUC(0) (infinity), terminal elimination rate constant (lambda(z)), volume of distribution in steady state (V-d(ss)), mean residence time (MRT), and clearance (Cl) were determined in each subject using the standard non-compartmental approach. In this study, the developed and validated lisinopril assay protocol in human plasma was performed using a C-8 analytical column and a mobile phase of 0.05M KH2PO4 (pH=2.75)-acetonitril-methanol (88:11:1, v/v/v) with the detection wavelength of 215 nm. Sample preparation consists of solid-phase extraction using commercially available C-18 cartridges. The method showed significant linear response-concentration relationship throughout the lisinopril concentration range of 0.01-0.2 mcg/ml, with the average within-run and between-run variations of 3.51 +/- 4.04 and 6.82 +/- 6.51 percent throughout the linear concentration range with corresponding average accuracy values of 96.78 +/- 3.55 and 97.30 +/- 3.33 percent, respectively. The average drug recovery from plasma was 94.70 +/- 3.05 percent throughout the linear concentration range. The limits of detection (LOD) and quantitation (LOQ) of the method were 5 and 10 ng/ml, respectively. The practical applicability of the method was proven throughout a bioequivalence study.