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Rationale: Direct analysis in real time is typically performed using helium as the ionisation gas for the detection of analytes by mass spectrometry (MS). Nitrogen and argon are found with abundance in the air and provide a cheaper and greener alternative to the use of helium as ionisation gas. This study explores the use of helium, nitrogen and argon as ionisation gas for the detection of organic compounds.Methods: Four illicit drugs, two amino acids and five explosives were chosen as target analytes to understand selectivity, sensitivity and linearity when helium, nitrogen or argon was used as the ionisation gas with the direct analysis in real time (DART) source. Analysis was carried out on a Waters Acquity QDa single quadrupole mass spectrometer.Results: Calibration curves over the range of 5-100 ng were produced for each analyte using the different ionisation gases to assess the instrument response.Nitrogen gave a higher response to concentration than helium or argon; however, the lowest limits of detection were observed when helium was used.Conclusions: All the target analytes were detected using DART-MS with helium, nitrogen or argon as the ionisation gas. Whereas helium provided the highest sensitivity, nitrogen produced reasonable limits of detection and had good linearity across the concentration range explored, suggesting it provides a greener and cheaper alternative to helium.

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