Investigational Study of Mesalamine Dissolution Discrepancy: Utilization of Hyphenated Ultrahigh Performance Liquid Chromatography‐Charged Aerosol Detection‐High‐Resolution Mass Spectrometry

Abstract

ABSTRACTPentasa (mesalamine/MSLM) is a widely prescribed delayed‐release capsule formulation for the treatment of inflammatory bowel disease. During dissolution study of Pentasa through ultraviolet (UV) spectroscopy, an unusual end‐release of about 110% has been observed. Initial liquid chromatography‐UV (LC‐UV) analyses of these dissolution samples confirmed three prominent peaks other than MSLM with a significant area percentage. Further systematic investigation was carried out by incubating active pharmaceutical ingredient in dissolution media for a longer duration and at elevated temperature followed by analysis through an inverse gradient LC‐charged aerosol detector (CAD). LC–high‐resolution mass spectrometry (HRMS) and online hydrogen‐deuterium exchange (HDX) mass spectrometry were also employed to identify and characterize these artifact products. The area % of prominent artifacts in LC‐UV was found to be way significant when compared to the area % obtained through inverse LC‐CAD, as CAD quantifies the peaks independent of the UV wavelength of absorbance. Inverse LC‐CAD was suitable to determine the relative response factor, whereas LC‐HRMS/MS and online HDX‐MS supported the characterization of these artifacts. These artifacts were found to be trimers, tetramers of MSLM formed due to polymerization, imparting additional pi‐bonds resulting in high UV absorptivity. These techniques when used in combinations serve complimentary to each other during such investigations.