Analysis of unstable degradation impurities of a benzodiazepine and their quantification without isolation using multiple linear regression

Publication date: Available online 17 January 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): John M. Campbell, Kaitie Grinias, Kevin Facchine, Benoît Igne, Jacalyn Clawson, John Peterson, Andy Wolters, Jeremy Barry, Simon Watson, Kevin LeachAbstractThis manuscript presents a novel methodology for calculating the relative response factors (RRFs) of unstable degradation impurities of molibresib (1). The degradation impurities were observed by HPLC during stress testing and were accompanied by large mass balance deficits. However, the impurities could not be isolated for traditional RRF determination due to their instability. The RRFs of two degradation impurities were determined without isolation by multiple linear regression analysis of HPLC-UV data. The results permitted accurate quantification of the degradants. The benefits and drawbacks of the approach are discussed, including suggested validation acceptance criteria.

Source: Journal of Pharmaceutical and Biomedical Analysis - January 17, 2019 Category: Drugs & Pharmacology Source Type: research