title: Stability of doripenem in reconstituted solution - thermal and oxidative decomposition kinetics and degradation products by LC-MS.
abstract: A ultra-fast liquid chromatography method applied to quantitation of doripenem in powder for injection was validated. Validation parameters were assayed and a rapid analysis was established by a reversed-phase system comprising a C18column endcapped (50 × 4.0 mm, 2.0 μm), mobile phase consisting of phosphoric acid 0.01% (pH 3.8) and acetonitrile (98:02, v/v) and a flow rate of 0.4 mL min-1. Drug stability was studied through submission to forced conditions, allowing the major degradation products to be detected and the kinetics parameters to be established. Thermal and oxidative degradation were determined, and indicated a kinetic decomposition following first and second order, respectively. The main degradation products were identified by LC-MS analysis, and the results were evaluated in order to suggest the chemical structures corresponding to respective masses and fragmentations. Six compounds were identified, with m/z 411, 427, 437, 634, 650 and 664. All of them resulted from cleavage of β-lactam ring and alcoholic chain and/or dimerization. These experimental results provide valuable information about the stability of doripenem reconstituted solution and procedures for its handling and storage.
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Pampa, BR 472 Km 585, CEP 97508-000, Uruguaiana, RS, Brazil.
authors.forename: Fábio
authors.initials: F
authors.lastname: de Souza Barbosa
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Pampa, BR 472 Km 585, CEP 97508-000, Uruguaiana, RS, Brazil.
authors.forename: José Pedro Etchepare
authors.initials: JPE
authors.lastname: Cassol
authors.affiliation: Laboratório de Desenvolvimento e Controle de Qualidade de Medicamentos, Universidade Federal do Pampa, BR 472 Km 585, CEP 97508-000, Uruguaiana, RS, Brazil.
authors.forename: Luiz Alcides das Chagas
authors.initials: LADC
authors.lastname: Batista
authors.affiliation: Laboratório de Desenvolvimento e Controle de Qualidade de Medicamentos, Universidade Federal do Pampa, BR 472 Km 585, CEP 97508-000, Uruguaiana, RS, Brazil.
authors.forename: Everson Willian Fialho
authors.initials: EWF
authors.lastname: Cordeiro
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, CEP 90610-000, Porto Alegre, RS, Brazil.
authors.forename: Marí Castro
authors.initials: MC
authors.lastname: Santos
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, CEP 90610-000, Porto Alegre, RS, Brazil.
authors.forename: Adriana Raffin
authors.initials: AR
authors.lastname: Pohlmann
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, CEP 90610-000, Porto Alegre, RS, Brazil.
authors.forename: Elfrides E S
authors.initials: EES
authors.lastname: Schapoval
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, CEP 90610-000, Porto Alegre, RS, Brazil.
authors.forename: Cássia Virginia
authors.initials: CV
authors.lastname: Garcia
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Pampa, BR 472 Km 585, CEP 97508-000, Uruguaiana, RS, Brazil.|Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, CEP 90610-000, Porto Alegre, RS, Brazil.
authors.forename: Andreas Sebastian Loureiro
authors.identifier: http://orcid.org/0000-0001-7991-7521
authors.initials: ASL
authors.lastname: Mendez
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D015780:Carbapenems / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D000077726:Doripenem; D004355:Drug Stability; D006358:Hot Temperature; D007700:Kinetics; D010084:Oxidation-Reduction; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000077726:Doripenem
keywords: LC-MS; UFLC method; decomposition kinetics; degradation products; doripenem