Analytical challenges and recent advances in the identification and quantitation of extractables and leachables in pharmaceutical and medical products.

Structure elucidation and quantitation of leachable impurities in pharmaceutical and medical products are crucial because unidentified and potentially toxic leachable impurities can pose health hazards to patients. Therefore, extractables and leachables (E&L) investigations have received significantly increased emphasis from regulatory agencies in recent years. Owing to the diverse chemical structures and properties of E&L compounds, various analytical challenges are encountered during their identification and quantification process. This review provides an overview of analytical challenges encountered during E&L analysis by LC-MS and GC-MS from an industrial standpoint along with the most recent advances in this field. Some of these challenges including Analytical Evaluation Threshold (AET), sample preparation, complex identification processes, and quantitation are discussed. Furthermore, the recent regulations have made analysis of E&L compounds more stringent in terms of lower AET, higher level of identification confidence and method validation requirements, necessitating the use of advanced analytical instrumentation and novel analytical approaches. • Analytical challenges and recent advances associated with E&L analysis are reviewed. • The most up-to-date information on analytical evaluation threshold is provided. • Challenges associated with common sample preparation techniques used during E&L analysis are summarized. • Comprehensive discussion on identification of E&L compounds by GC-MS and LC-MS is provided. • Detailed discussion is provided on quantitation of E&L compounds and approaches to address associated challenges. [ABSTRACT FROM AUTHOR]