Development of a rapid liquid chromatography tandem mass spectrometry method for the determination of lisinopril, applicable for a bioequivalence study, employing a 96-well format solid phase extraction protocol Original Research Article

A rapid liquid chromatography/tandem mass spectrometry (LC/MS-MS) method was developed for the determination of lisinopril in human plasma. Lisinopril and the internal standard enalaprilat (IS) were extracted from human plasma by semi-automated solid phase extraction (SPE) using a 96-well format extraction plate. Initially, a 1:1 plasma: acetonitrile (ACN) mixture was prepared and vortexed to achieve protein precipitation. After centrifugation, an aliquot of the supernatant water/ACN solvent mixture was evaporated. The residue was dissolved in a certain volume of a reconstitution solution, which was passed through the extraction plate and the eluent was analyzed by combined reversed phase liquid chromatography tandem mass spectrometry with positive ion electrospray ionization using multiple reactions monitoring (MRM). The method was proved to be sensitive and specific for both drugs and its statistical evaluation revealed excellent linearity for the range of concentrations 2.0–200.0 ng mL−1 and very good accuracy, and inter- and intraday precisions. The proposed method enables the rapid and reliable determination of lisinopril in pharmacokinetic or bioequivalence studies after per os administration of 20 mg tablet formulations of lisinopril and it was applied in such study from our laboratory.