ISOLATION, CHARACTERIZATION OF DEGRADATION PRODUCTS OF SITAGLIPTIN AND DEVELOPMENT OF VALIDATED STABILITY-INDICATING HPLC ASSAY METHOD FOR SITAGLIPTIN API AND TABLETSAbstract
The degradation pathway of sitagliptin in bulk and tablet has been investigated during stress study. Major degradation products were isolated in pure form and characterized using mass and NMR spectroscopy. Three previously unreported impurities were found to be, 3-(trifluoromethyl)-6, 7-dihydro[1,2,4]triazolo[4, 3-a]pyrazin-8(5H)-one, (2E)-1-[3-(trifluoromethyl)-5, 6-dihydro[1, 2, 4]triazolo[4, 3-a]pyrazin-7(8H)-yl]-4-(2, 4, 5-trifluorophenyl)but-2-en-1-one and (3E)-1-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4, 3-a]pyrazin-7(8H)-yl]-4-(2, 4, 5-trifluorophenyl)but-3-en-1-one. Further, a stability-indicating reverse phase HPLC assay method was developed on Poroshell 120 EC-C18 (3X150mm, 2.7µ) column using mobile phase consisting of 5mM ammonium acetate and acetonitrile with gradient elution in presence of spiked degradation products and impurity. The flow rate was 0.5ml/min and detection was at 210nm. The method was found to be linear over 10µg-500µg/ml (r2>0.999). The method was validated with respect to accuracy, precision, specificity, robustness and found to be stability indicating.
Dnyaneshwar P. Sonune and Mahesh Kumar Mone*
Drug Discovery Facility, Advinus Therapeutics Ltd, Quantum Towers, Plot-9, Rajiv Gandhi Infotech Park, Phase-I, Hinjewadi, Pune-411 057, Maharashtra, India
29 April, 2013
23 June, 2013
19 August, 2013
01 September, 2013