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. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

The importance of elucidating the structure and quantifying leachable impurities in pharmaceutical and medical products has received increased emphasis from regulatory agencies. The industrial sector faces various analytical challenges in E&L analysis, including AET, sample preparation, complex identification processes, and quantitation. Recent regulations have made the analysis of E&L compounds more stringent, requiring the use of advanced analytical instrumentation and novel analytical approaches.