Venturi Easy Ambient Ionization Mass Spectrometry Coupled to Gas Chromatography for High-Throughput Quantitation of Acetic Acid Residues in Pharmaceuticals

Gas chromatography coupled to mass spectrometry (GC-MS) is a robust and well-established technique for the analysis of volatile organic compounds (VOCs). Typically, electron ionization is used to combine these techniques; however, it requires high-vacuum conditions and produces extensive fragmentation. Venturi easy ambient sonic spray ionization (V-EASI) mass spectrometry is an ambient ionization approach suitable for samples in both solution and gas phases, employing high pressure as a soft ionization mechanism. In this work, we present a proof-of-principle for coupling GC to MS via V-EASI, applied to the quantification of acetic acid as a residual solvent in pharmaceutical products for quality control purposes. The system was automated and optimized, achieving a runtime of approximately 70 s per sample. The developed method meets the validation guidelines established by the International Council for Harmonization (ICH). Owing to its speed, simplicity, and broad applicability, GC-V-EASI-MS represents a powerful alternative for real-time, high-throughput VOC analysis.