Features of enalapril distribution in the body of warm blooded animals (rats)

Abstract

Enalapril is a drug from the group of angiotensin converting enzyme inhibitors. Objective: to study the distribution characteristics of enalapril in the body of warm-blooded animals (rats) with normal renal excretory function and in conditions of its impairment. Materials and methods. The analyte was enalapril (N-[N-[(1S)-3-phenyl-1-(ethoxycarbonyl)propyl]-L-alanyl]- L-proline maleate). The analyte was isolated from biomatrices by infusion. Semi-preparative column chromatography was used for the purification of enalopril, and TLC, HPLC and spectrophotometric methods were used for the determination. Results. To isolate the analyte, a mixture of acetone-methanol (4:6) was proposed; the analyte was purified in a column (150×10 mm) of Silasorb S-8 sorbent (eluent isopropanol-water (9:1)), determined on Sorbfil PTSKh plates -AF-B-UV (eluent - ethanol), by absorption of UV light in ethanol and by HPLC (Luna® 5 µm C-18 100A 250. 0×4.0 mm column; eluent - methanol-acetonitrile-phosphate buffer with pH=3 (40:5:55)). After poisoning of rats with enalapril (LD50×3), the predominant presence of the analyte in healthy animals was found in the lungs (61.7 ± 5.0), small intestine with contents (46.5±5.1), stomach with contents (43.6±5.0), blood (43.1±4.1), in animals with impaired renal excretory function - in kidneys (154.4±18.6), blood (52.6±2.2), stomach with contents (41.9±3.7), small intestine with contents (36.8±6.6). Conclusion. Impairment of renal excretion leads to a change in the localisation of enalapril in the body and a significant increase in the presence of the toxicant in the blood, kidneys and spleen.