Toward Metabolomics Analyses With Combined Capillary Vibrating Sharp‐Edge Spray Ionization and Atmospheric Pressure Chemical Ionization

RATIONALE: The varied properties of metabolomics components dictate the tools used in mass spectrometry (MS) characterization including the selection of the ionization source. However, the ionization of select compounds limits characterization efficiency. A simple setup employing vibrating sharp-edge spray ionization (VSSI) accesses two distinct ionization processes that can be performed cyclically during LC. METHODS: The MS approach described here couples analyte sample nebulization by VSSI with corona discharge to achieve ionization via an atmospheric pressure chemical ionization (APCI)-like process. A 28-component small molecule standard mixture as well as a C. elegans metabolite extract are analyzed to determine potential for utilization in metabolomics experiments. RESULTS: For the standard panel, the cVSSI-APCI approach is shown to better ionize half of all compounds compared to ESI. For the metabolomics extract, cVSSI-APCI is shown to significantly outperform ESI for multiple compounds across a range of reversed-phase LC solution conditions, while ESI is shown to outperform cVSSI-APCI for other species. Manual cycling between field-enabled cVSSI and cVSSI-APCI ionization processes results in relatively rapid equilibration to distinct ionization processes with high reproducibility in compound ionization. CONCLUSION: Cycling between ionization processes is accomplished on a timescale suitable with longer timescale LC runs. To obtain sufficient cycling rates for high-throughput metabolomics experiments (~10 to 20 min) will require the use of high-voltage, high-power pulser electronics. The preliminary results suggest such an approach will be successful for online analyses.