Recent Advances in Stability Studies of Carbapenems

The carbapenems are a class of a β-lactam antibiotics with a broad spectrum of antibacterial activity. In all carbapenems, a β-lactam ring is required for their antibacterial activity. In addition, the bi-cyclic 4:5 fused ring is one of the main reasons for the instability of carbapenems. The 2C, 3C and 6C substituents affect the spectrum of microbiological activity, pharmacokinetic parameters, enzymatic and chemical stability. The early carbapenems (imipenem, panipenem) were degraded by renal dihydropeptidase (DHP-I) and required co-administration with DHP-I inhibitors to prevent this inactivation. The newer carbapenems (meropenem, ertapenem, doripenem and biapenem) with a 1β-methyl group at 4C are stable to DHP-I hydrolysis. The carbapenems are still susceptible to chemical degradation under the influence of different stress factors (temperature, humidity, light, oxidizing, hydrogen concentration) in aqueous solutions and solid state. This paper provides an overview of recent observations on the degradation kinetics of carbapenems used in therapy, their mechanisms of degradation, general and specific acid-base hydrolysis, catalytic effect of buffers and thermodynamic parameters describing the degradation of carbapenems in aqueous solutions and solid state. As during the degradation of carbapenems depending on stress factors (solvents, pH, drug concentration, temperature, time) various degradation products are formed, their chemical structures and pathways of their formation are also compared. Keywords: Carbapenems, Stability-indicating analytical method (SIAMs), Related substances, Stability in aqueous solutions and in solid state, beta-lactam antibiotics, Pharmacokinetic parameters, Chemical stability, Degradation, HPLC, DAD detection