An isocratic reversed-phase liquid chromatography (RP-LC) method has been developed and validated for the quantitative determination of tebipenem, a novel β-lactam antibiotic. The method was designed to assess the stability of tebipenem under various stress conditions, including acidic and basic hydrolysis, oxidation, thermal degradation, and photolysis. A C-18 stationary phase coupled with a mobile phase composed of 12 mM ammonium acetate and acetonitrile (96:4, v/v) enabled efficient separation of tebipenem from its degradation products. Chromatographic analysis was performed using a PDA detector set at 298 nm, with a flow rate of 1.2 mL/min. The method demonstrated excellent linearity over the concentration range of 0.041–0.240 mg/mL, with a correlation coefficient (r) of 0.999. Precision was confirmed through repeatability (intra-day RSD: 1.14–1.96%) and intermediate precision (inter-day RSD: 2.05%), while recovery rates ranged from 99.60% to 101.90%, indicating high accuracy. The limits of detection and quantification were determined to be 9.69 μg/mL and 29.36 μg/mL, respectively.
Stress degradation studies revealed that tebipenem is highly susceptible to alkaline conditions, with complete degradation observed within one minute in 0.05 N NaOH at room temperature. In contrast, acidic hydrolysis (0.2 N HCl, 303 K) and oxidative degradation (3% H₂O₂, 298 K) led to approximately 40–65% degradation after short exposure times.3-Phenylpropyl Data Sheet Thermal degradation was more pronounced under high humidity (76.5% RH, 343 K), resulting in 50.45% degradation after 45 minutes, while dry air (0% RH, 373 K) caused 45.34% degradation after 72 hours. No significant degradation occurred during photolytic exposure under sunlight (10,000 lux, 48 h). Chromatograms showed distinct new peaks only under oxidative conditions, suggesting the formation of oxidized degradation products.Telmisartan impurity 1 site The absence of detectable degradation peaks in other conditions may be attributed to the lack of chromophores suitable for UV-PDA detection.PMID:35038271
To understand the molecular basis of reactivity, quantum chemical calculations based on density functional theory (DFT) were performed. The HOMO and LUMO orbital distributions indicated that electron-rich regions are localized on the 1-[(1,3-thiazolin-2-yl)azetidin-3-yl]thio substituent, suggesting this site plays a key role in electron transfer during acid-catalyzed and oxidative degradation. The LUMO was primarily located on the fused 4:5 β-lactam–pyrrolidine ring system, highlighting its vulnerability to nucleophilic attack. These findings support the hypothesis that the degradation pathway involves initial electron migration followed by ring opening. The developed method proved selective, robust, and sensitive, making it suitable for routine quality control and stability testing of tebipenem formulations. This study demonstrates the power of combining chromatographic analysis with computational chemistry to elucidate degradation mechanisms in complex pharmaceuticals.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com