Platform analytical procedure for the analysis of residual solvents in active pharmaceutical ingredients by headspace-gas chromatography - A use case of implementation.

The determination of residual solvents in active pharmaceutical ingredients (APIs) is often a regulatory requirement. Residual solvents physicochemical properties remain consistent across different APIs. This analysis is well-suited for the creation of a platform analytical procedure. This study developed a robust headspace gas chromatography (HS-GC) analytical procedure based on the enhanced approach as outlined in the ICH Q14 for the analysis of residual solvents in APIs. Method development was driven by a clear and concise analytical target profile (ATP), ensuring that performance characteristics were aligned with quality attributes. A platform analytical procedure capable of quantifying 18 residual solvents, resolving a critical pair, was successfully created. A quality-by-design approach was employed for some of the HS settings, and a method operable design region (MODR) was successfully created and confirmed. Method validation focused on the performance characteristics that do not require a sample matrix. Specificity, range (linearity and quantitation limit) and reference solution stability were successfully validated. Finally, a framework for the adoption of the platform for the analysis of residual solvents in a specific product was created and the regulatory implications were discussed. Overall, this work demonstrates that platform analytical procedures can be effectively developed and implemented while making use of the creation of MODR and ensuring compliance with regulatory requirements. This work lays the foundation and provides a structured approach for the creation of analytical platforms, removing some of the uncertainty and facilitating the broader pharmaceutical industry adoption.