Identification and structure elucidation of a new degradation impurity in the multi-component tablets of amlodipine besylate.

Graphical abstract Highlights • New unknown impurity was observed during the accelerated stability analysis in the tablets of amlodipine besylate. • UHPLC-MS and NMR techniques were employed to identify and to fully characterize this degradation compound. • The impurity is 3-ethyl 5-methyl 4-(2-chlorophenyl)-6-methyl-2-(morpholin-2-yl)-1,4-dihydropyridine-3,5-dicarboxylate. Abstract New unknown impurity at m/z 421.15 was observed during the accelerated stability analysis (40 °C/75% relative humidity) in the multi-component tablets of amlodipine besylate by reversed-phase ultra-high performance liquid chromatography–mass spectrometry (UHPLC–MS). UHPLC–MS and nuclear magnetic resonance (NMR) techniques were employed to identify and fully characterize the degradation compound. The degradation product was unambiguously identified as 3-ethyl 5-methyl 4-(2-chlorophenyl)-6-methyl-2-(morpholin-2-yl)-1,4-dihydropyridine-3,5-dicarboxylate and mechanism of its formation was proposed. It was confirmed that the degradation product was formed by the reaction of amlodipine with formaldehyde originating from the excipients present in the dosage form. [ABSTRACT FROM AUTHOR]