Impurity profiling, chiral analysis, uhplc method development and validation of pharmaceutical compounds

Abstract

Two drug substances namely pentoxifylline and triprolidine were subjected to various stress conditions and their degradation profile was studied with conventional LC-MS. Interestingly, these compounds under went distinct transformation giving rise to degradation products. These degradation products from alkali and oxidative degradation were isolated and purified with preparative HPLC. The structures of these products was elucidated using 1D, 2D NMR spectroscopy and high resolution mass spectrometry (Q-TOF LC/MS). A novel gem-dihydroperoxide, namely 1-(5,5-Bis-hydroperoxy-hexyl)-3,7-dimethyl-3,7-dihydro-purine-2,6-dione was identified as an oxidative degradation product of pentoxifylline. Two major base hydrolysis products which were reported earlier were also isolated and identified. Two oxidative degradation products of triprolidine were identified to be Triprolidine N-Oxide and Pyridin-2-yl-p-tolyl-methanone. An efficient stability indicating UHPLC separation methods were developed for pentoxifylline and triprolidine along with their degradation products, using 1.8 and#956;m, C18 reverse phase column. Baseline separation was achieved with a run time of four minutes. The analytical methods were validated with respect to system suitability, specificity, linearity, range, precision, accuracy and robustness. newlineOne very critical property of the drug molecule, which makes a huge impact on its physiological properties, is its chirality . Increased throughput of medicinal chemistry in the drug discovery field has substantially increased production of chiral new chemical entities (NCEs) and intermediates with diverse structural features, requiring fast chiral screening strategies. In an effort to explore more versatile and reliable fast chiral separation screening methods we have developed newlineand evaluated flow gradients and mobile phase gradients in polar organic and normal phase modes on three popular chiral stationary phases namely polysaccharide coated