METHOXYAMINE-BASED DERIVATIZATION FOR TRACE-LEVEL CARBONYL COMPOUND ANALYSIS USING LC-MS/MS

Carbonyl compounds, including aldehydes and ketones, are ubiquitous environmental pollutants and potential genotoxic impurities in pharmaceutical formulations. Their volatility, instability, and reactivity necessitate derivatization for reliable detection and quantification. In this study, methoxyamine hydrochloride was employed as a derivatizing agent to convert carbonyl compounds into stable oxime derivatives, which were subsequently analyzed using LC-MS/MS and GC-MS techniques. The method was optimized with Chromatopak Peerless C18 column under APCI ionization conditions, achieving high sensitivity with detection limits as low as 0.1 ng/mL for acetophenone and 1 ng/mL for benzophenone. Validation parameters including linearity, accuracy, precision, and recovery demonstrated compliance with accepted analytical criteria (R² > 0.99, %RSD < 5%). The developed method enables robust identification and quantification of trace-level carbonyl impurities in pharmaceutical formulations, thereby supporting impurity profiling and ensuring drug safety. This approach highlights the importance of sensitive analytical techniques in monitoring genotoxic impurities and mitigating drug–excipient incompatibilities.