To Synthesize and Characterize Metabolite Enalapril: PKPD and Toxicity Predictions by Computational Approaches

Abstract

Enalapril is a prodrug that facilitates the transformation of angiotensin I to angiotensin II, an ingredient that brings constriction of blood vessels by action of the enzyme angiotensin-converting enzyme (ACE). Reversed-phase high-performance liquid chromatography (RP-HPLC) method is the focus of this work, which also includes its characterization, optimization, and synthesis. The objective is to correctly, precisely, and sensitively determine both enalapril and its synthesized metabolite, enalaprilat, when present as an impurity. The paper also forecasts the ADME and toxicity characteristics of ENLP by utilizing several ADME databases, including SWISS ADME and molesoft. The laboratory synthesized enalaprilat, the metabolite derived from enalapril, and characterized. The Kinetex C18 stationary phase was employed in the analytical approach. Flow rate was 1.0 mL/min, and the injection volume was 20 μL. With a wavelength of 244 nm, the run lasted for 10 minutes. The mobile phase used was an 80% acetonitrile: 20% pH 3 phosphate buffer. The HPLC technique validation, which involved the identification of the enalapril metabolite, followed the parameters outlined in ICH Q2B (R1). The analysis exhibited a range of accuracy and precision between 98.75 and 102.5% for all substances being tested. This approach is appropriate for identifying and measuring the metabolite in enalapril bulk or formulations. The method for assessing enalaprilat in biological fluids has the potential to be further refined and applied in clinical and bioequivalence research. The study furthermore presents an evaluation of toxicity utilizing computational methods such as the Swiss tool, with the objective of aiming to mitigate potential risks.