Characterization of four major degradation products in metformin by 2D LC-QTOF/MS/MS

Abstract

A two-dimensional liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(2D LC-QTOF/MS/MS) method was developed for the characterization of four major degradation products in metformin under acidic, basic, oxidative and 6 months accelerated conditions. A CAPCELL PAK SCX TYPE UG80 column(5 μm, 4.6 × 150 mm) was applied using 17 g/L ammonium dihydrogen phosphate adjusted to pH 3.0 by phosphoric acid as the mobile phase at a flow rate of 1.0 mL/min in the first dimension (D1), and the collected fractions further flowed to a Waters Xbridge C18 column(5 μm, 4.6 mm × 250 mm) with a mobile phase consisting of 0.1 % formic acid and acetonitrile (95:5 v/v) at the same flow rate as the second dimension(D2). Two of the impurities were never reported as the degradation of metformin, and all the four structures, as well as the proposed fragmentation patterns were inferred in this research.

Keywords: 2D LC-QTOF/MS/MS; Degradation products; Impurities; Stressed degradation.