Characterization of mass ionizable degradation products of gliclazide by LC/ESI-MS

A solution containing six UV active degradation products (I-VI) of gliclazide formed under different stress conditions prescribed by International Conference on Harmonisation is analyzed by LC/ESI-MS. Of the six, four products I, II, V, and VI are detected in MS. The molecular weights of these are 171, 229, 337, and 321, respectively. The comparison of their mass fragmentation pattern with the drug has helped in establishment of their structures. These are identified as p-tolylsulfonamide (I), methyl N-(p-tolylsulfonyl)carbamate (II), 4,4a,5,6,7,7a-hexahydro-3H-cyclopenta[d]pyridazin-1-yl N-(p-tolylsulfonyl)carbamate (V), and N-(4,4a,5,6,7,7a-hexahydro-3H-cyclopenta[d]pyridazine-1-carbonyl)-4-methyl benzenesulfonamide (VI). It is indicated that product II is not a true degradation product, but a methyl ester formed in the presence of methanol, used to solubilize the drug in reaction solutions. Another product, which is not detected in LC/UV but showed up in the LC/MS chromatogram, is identified as (2-diazenylmethyl)cyclopentyl-methanol (VII). The pathways for the formation of these products are proposed.