LC-UV-PDA and LC-MS studies to characterize degradation products of glimepiride

Degradation products of glimepiride formed under different forced conditions have been characterized through LC-UV-PDA and LC-MS studies. Glimepiride was subjected to forced decomposition under the conditions of hydrolysis, oxidation, dry heat and photolysis, in accordance with the ICH guideline Q1A(R2). The reaction solutions were chromatographed on reversed phase C8 (150 mm x 4.6 mm i.d., 5 p,m) analytical column. In total, five degradation products (I-V) were formed under various conditions. The drug degraded to products II and V under acid and neutral hydrolytic conditions while products 1, 111 and IV were formed under the alkaline conditions. The products II and V were also observed on exposure of drug to peroxide. No additional degradation product was shown up under photolytic conditions. All the products, except 1, could be characterized through LC-PDA analyses and study of MS fragmentation pattern in both +ESI and -ESI modes. Product 1 could not be identified, as it did not ionize under MS conditions. The products 11, 111 and V matched, respectively, to impurity B (glimepiride sulfonamide), impurity J and impurity C (glimepiride urethane) listed in European Pharmacopoeia. The product IV was a new degradation product, characterized as [[4-[2-(N-carbamoyl)aminoethyl]phenyl]sulfonyl]-3-trans-(4-methylcyclohexyl) urea. The degradation pathway of the drug to products (I-V is proposed, which is yet unreported. (C) 2008 Elsevier B.V. All rights reserved.