Analytical instability and aqueous degradation of carbapenem antibiotics: formation of β-lactam-retaining transformation products

Carbapenems are last-resort antibiotics used to treat severe infections caused by multidrug-resistant bacteria. Despite their clinical importance and documented consumption, they remain largely undetected in environmental monitoring studies. This study investigated whether the lack of detection of carbapenems in environmental studies reflects analytical limitations, rapid degradation, or both. Sensitive LC-MS/MS methods were developed for selected carbapenems and used to assess compound stability under analytical and environmentally relevant conditions. All investigated carbapenems exhibited limited stability, with degradation strongly accelerated by methanol. Under environmentally relevant conditions, parent compounds degraded rapidly in river water, biofilm-containing water, and UV-exposed water, with little difference between treatments. High-resolution LC-MS/MS analysis revealed formation of multiple transformation products (TPs) retaining an intact β-lactam ring. Meropenem generated four β-lactam-retaining TPs, and faropenem generated four, several of which remained detectable long after disappearance of the parent compounds. These findings help explain the lack of detection of carbapenems in environmental surveys and demonstrate that disappearance of parent compounds does not necessarily imply elimination of β-lactam-containing structures. The persistence of β-lactam-retaining TPs suggests that environmental exposure and associated selective pressure may persist after parent carbapenems have degraded, highlighting the need for further investigation of their biological activity and potential role in antimicrobial resistance.