Primary degradation of antidiabetic drugs

Abstract

Type 2 diabetes is a chronic disease affecting a large portion of the world population and is treated by orally administered drugs. Since these drugs are often taken in high doses and are excreted unchanged or partially metabolised many of them are nowadays detected in surface waters or wastewater treatment plants effluents. Unmetabolised antidiabetics or some of their transformation products retain their pharmacological activity, therefore their presence in the environment is highly undesired. One of the main routes of elimination from wastewaters or surface waters is biodegradation. Within this work we tested primary biodegradation of: metformin and its metabolite guanylurea, acarbose, glibenclamide, gliclazide and glimepiride. We also inspected what might be the extent of the degradation by examining the products formed during the degradation using liquid chromatography coupled to tandem mass spectrometry. Transformation of diabetes staple drug metformin to dead-end product guanylurea was generally confirmed. An alternative, though rather minor pathway leading to complete mineralisation was also found. Complete primary degradation was observed for acarbose, glibenclamide and glimepiride whereas gliclazide was shown to be resistant to biodegradation. These results allow a preliminary assessment of environmental persistency of a very important group of pharmaceuticals and show need for implementing monitoring programs.

Keywords: Antidiabetic drugs; Environmental fate; Pharmaceuticals; Primary biodegradation; Sulphonamides.