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Stability of doripenem in reconstituted solution – thermal and oxidative decomposition kinetics and degradation products by LC–MS
Author(s) -
Souza Barbosa Fábio,
Cassol José Pedro Etchepare,
Batista Luiz Alcides das Chagas,
Cordeiro Everson Willian Fialho,
Santos Marí Castro,
Pohlmann Adriana Raffin,
Schapoval Elfrides E. S.,
Garcia Cássia Virginia,
Mendez Andreas Sebastian Loureiro
Publication year - 2017
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.3940
Subject(s) - chemistry , doripenem , chromatography , degradation (telecommunications) , kinetics , forced degradation , decomposition , chemical decomposition , phosphoric acid , chemical stability , high performance liquid chromatography , organic chemistry , reversed phase chromatography , biochemistry , telecommunications , physics , antibiotic resistance , imipenem , quantum mechanics , computer science , antibiotics
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 C 18 column 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.