CHEMICAL STABILITY STUDIES OF PROPARGYLAMINE-CONTAINING DRUGS

The interest regarding this class of drugs arises from the analyses in the course of stability studies performed on new formulations of oxybutynin hydrochloride (OXY), a tertiary propargylamine used for the management of urinary frequency, urgency and incontinence in neurogenic bladder disorders. During the study, a new and unprecedented degradation product was identified in topical formulations, whose structure and mechanism of formation has been determined through a forced degradation study [1]. These results prompted us to extend the study to other propargylamine-containing drugs. Selegiline (SG, tertiary and H-terminated propargylamine) and rasagiline (RG, secondary and H-terminated propargylamine), MAO-B inhibitors used in the treatment of Parkinson’s Disease, were included in the panel of compounds to increase the chemical diversity of propargylamine moiety. To face the analytical tasks, required in performing the chemical stability studies, LC-DAD-UV and LC-ESI-MS/MS techniques were employed: the assignment of all degradation product structures was based on LC-ESI-MS/MS analysis and confirmed by comparison with reference standard obtained by synthesis. The analytical methods were developed and validated to allow both qualitative and quantitative determination of analytes. Moreover the new degradation products showing in their structure the presence of a structural alert were assessed for genotoxic potential evaluation.