SIMULTANEOUS DETERMINATION OF PERINDOPRIL AND PERINDOPRILATE IN PLASMA: DEVELOPMENT AND VALIDATION OF TECHNIQUES

Introduction. Angiotensin-converting enzyme inhibitors, perindopril in particular, are used to prevent and treat cardiovascular diseases. To confirm the quality of generic drugs, there is a need for techniques for the simultaneous determination of the active substance itself and its active metabolite perindoprilate. Objective: to develop a simple, reliable, and reproducible technique for simultaneous isolation of perindopril and perindoprilate from plasma and for their quantification using high performance liquid chromatography-mass spectrometry (HPLC-MS). Material and methods. The investigation used the substance perindopril erbumine and the standard perindoprilate and enalapril maleate as an internal standard. The investigation was conducted on a Dionex Ultimate 3000 HPLC with a Bruker micrOTOF-QII mass detector on cartridges for solid-phase extraction (SPE) using an Isolute C18-500 mg column. Chromatograms were processed and a calibration curve was constructed automatically by the Quant Analysis program. Results. A highly selective technique for simultaneous isolation and quantitative determination of perindopril and perindoprilate in plasma, by using SPE on C18 cartridges and HPLC-MS detection, was developed and validated. The total time of chromatographic analysis was 6 min. The lower limits for quantitative determination of perindopril and perindoprilate in plasma are 0.4 and 1.5 ng/ml, respectively. Conclusion. The developed technique is suitable for pharmacokinetic studies and determination of the bioavailability and bioequivalence of perindopril-based drugs