title: Stress Degradation Studies of Tebipenem and a Validated Stability-Indicating LC Method.
abstract: A inexpensive and rapid isocratic LC method has been developed for the quantitative determination of tebipenem-a new β-lactam antibiotic. Stress degradation studies were performed on tebipenem in acidic (0.2 N hydrochloric acid) and basic (0.02 N sodium hydroxide) solutions, in a solution with oxidizing agent (3 % hydrogen peroxide), and in the solid state, during thermolysis and photolysis. For a chromatographic separation of tebipenem and its degradation products, a C-18 stationary phase and 12 mM ammonium acetate-acetonitrile (96:4 v/v) were used. A quantitative determination of tebipenem was carried out by using a PDA detector at 298 nm, with a flow rate of 1.2 mL min-1. The linear regression analysis for the calibration plots showed a good linear relationship (r= 0.999) in the concentration range 0.041-0.240 mg mL-1. The method demonstrated good precision (1.14-1.96 % RSD) and recovery (99.60-101.90 %). The limits of detection and quantitation were 9.69 and 29.36 μg mL-1, respectively. The analysis of tebipenem reactivity was supported by quantum chemical calculations based on the density functional theory (DFT). The analysis of the electron density of the HOMO and LUMO of tebipenem suggested the possibility of electron transport in the molecule during the degradation of bi-cyclic 4:5 fused penem rings.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland.
authors.forename: Judyta
authors.initials: J
authors.lastname: Cielecka-Piontek
authors.forename: Przemysław
authors.initials: P
authors.lastname: Zalewski
authors.forename: Bolesław
authors.initials: B
authors.lastname: Barszcz
authors.forename: Kornelia
authors.initials: K
authors.lastname: Lewandowska
authors.forename: Magdalena
authors.initials: M
authors.lastname: Paczkowska
keywords: Column liquid chromatography; HOMO–LUMO; Intramolecular charge transfer; Stress degradation studies; Tebipenem
references.citation: J Pharm Biomed Anal. 2002 Jun 15;28(6):1011-40
references.pmid: 12049968
references.citation: Drugs. 2007;67(7):1027-52
references.pmid: 17488146
references.citation: J Pharm Biomed Anal. 2008 Jan 7;46(1):52-7
references.pmid: 17936535
references.citation: Antimicrob Agents Chemother. 2008 Jun;52(6):2053-60
references.pmid: 18391040
references.citation: Antimicrob Agents Chemother. 2005 Mar;49(3):889-94
references.pmid: 15728880
references.citation: Mol Pharm. 2010 Oct 4;7(5):1747-56
references.pmid: 20735088
references.citation: Jpn J Antibiot. 2009 Apr;62(2):116-26
references.pmid: 19673353
references.citation: Drug Metab Pharmacokinet. 2008;23(6):434-46
references.pmid: 19122338