Stability in clinical use and stress testing of meropenem antibiotic by direct infusion ESI-Q-TOF: Quantitative method and identification of degradation products

Publication date: Available online 6 November 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Fábio de Souza Barbosa, Leonardo Capra Pezzi, Marisa Tsao, Sandra Manoela Dias Macedo, Tiago Franco de Oliveira, Elfrides E.S. Schapoval, Andreas S.L. MendezAbstractAn ESI-MS/MS method through direct infusion was validated for quantitative analysis of meropenem powder for injection. The validation parameters were established in a rapid analysis of 30 s. Drug stability was studied through the submission to stress testing, resulting on four degradation products. Under hydrolytic conditions, in acid, neutral and alkaline media, the major degradation product was formed through the cleavage of the β-lactam ring. Oxidation of the drug using H2O2 (3%) showed the formation of two degradation products from a decarboxylation reaction and N-oxide formation. Under high humidity conditions, there was detected a dimer product. The stability of meropenem after reconstitution was studied in conditions that simulate its clinical use. In samples reconstituted and diluted in infusion fluids, an extensive degradation was observed. At room temperature meropenem maintained its content> 90% for up to 4 h when prepared in 5% glucose and for up to 12 h when prepared in 0.9% NaCl. Through ESI-MS/MS analyzes it was observed a degradation product formed by β-lactam ring cleavage, detected in all conditions studied. It was also identified a degradation product formed only in 5% g...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research