enalapril and acetonitrile

Green bioanalytical approaches are oriented toward minimization or elimination of hazardous chemicals associated to bioanalytical applications. LC/MS-MS assay of enalapril and enalaprilat in human plasma was achieved by elimination of acetonitrile from both sample preparation and chromatographic separation stages. Protein precipitation (PP) by acetonitrile addition was replaced by liquid-liquid extraction (LLE) in 1-octanol followed by direct large volume injection of the organic layer in the chromatographic column operated under reversed phase (RP) separation mechanism. At the mean time, acetonitrile used as organic modifier in the mobile phase was successfully replaced by a mixture of propylene carbonate/ethanol (7/3, v/v). Three analytical alternatives ((I) acetonitrile PP+acetonitrile based chromatographic elution; (II) 1-octanol LLE+acetonitrile based chromatographic elution; (III) 1-octanol LLE+propylene carbonate/ethanol based chromatographic elution) were validated and the quality characteristics were compared. Comparison between these alternative analytical approaches was also based on results obtained on incurred samples taken during a bioequivalence study, through application of the Bland-Altman procedure.

Topics: 1-Octanol; Acetonitriles; Chromatography, Liquid; Cross-Over Studies; Enalapril; Enalaprilat; Ethanol; Green Chemistry Technology; Humans; Linear Models; Liquid-Liquid Extraction; Propane; Randomized Controlled Trials as Topic; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry; Therapeutic Equivalency; Water

Stability of enalapril maleate formulations can be affected when the product is exposed to higher temperature and humidity, with the formation of two main degradation products: enalaprilat and a diketopiperazine derivative. In this work, stability and drug release profiles of 20 mg enalapril maleate tablets (reference, generic and similar products) were evaluated. After 180 days of the accelerated stability testing, most products did not exhibit the specified amount of drug. Additionally, drug release profiles were markedly different from that of the reference product, mainly due to drug degradation. Changes in drug concentration and drug release profile of enalapril formulations are strong indicators of a compromised bioavailability, with possible interferences on the therapeutic response for this drug.

Topics: Acetonitriles; Angiotensin-Converting Enzyme Inhibitors; Biological Availability; Buffers; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Dosage Forms; Drug Stability; Enalapril; Guidelines as Topic; Humidity; Hydrogen-Ion Concentration; In Vitro Techniques; Molecular Structure; Pharmacopoeias as Topic; Phosphates; Powders; Reference Standards; Solubility; Tablets; Temperature; Therapeutic Equivalency