HPLC/MS DETERMINATION OF ENALAPRIL AND ENALAPRILAT IN THE BLOOD PLASMA

A reproducible and sensitive analytical procedure has been developed for the quantitative determination of enalapril and enalaprilat in the blood plasma by high-performance liquid chromatography with mass-spectrometric detection (HPLC/MS). For increasing the sensitivity and reproducibility of analyses, the samples were treated with diazomethane in order to obtain methyl esters of the analyzed compounds. The quantitative determination was carried out using the internal standard method; the internal standard was captopril. The detection was performed in the positive ion mode for ions with m/z = 377 (enalaprilat methyl ester), 391 (enalapril methyl ester), and 267 (captopril methyl ester). Enalapril, enalaprilat, and captopril were isolated from the blood plasma and purified by means of solid-phase extraction. The calibration plot is linear in the concentration range from 0.5 to 200 ng/ml. The detection limits for both enalaprilat and enalapril in the blood plasma are 0.1 ng/ml.