Enhanced Sensitivity and Isomer Differentiation of Alkyl Nitrites Using a Pulsed DC SPI-MS

Despite their significance as forensic targets, alkyl nitrites, classified as illegal drugs, have received little attention in forensic analysis due to their high volatility and chemical instability. Here, we present a high-performance analytical approach using a pulsed dc soft plasma ionization-quadrupole mass spectrometry (pulsed dc SPI-MS) system, uniquely designed to operate using ambient air as the discharge gas. In this system, the modulation of the duty ratio functions as a “structural probe” to identify reactive isomers. Unlike conventional dielectric barrier discharge (DBD) sources that typically operate at atmospheric pressure, our SPI system utilizes a controlled pressure regime of several kPa, where the nitrogen in the ambient air effectively functions as a third-body gas to suppress excessive internal energy. The control of the duty ratio in our pulsed dc SPI source allowed for the successful manipulation of ion–molecule reaction pathways for highly reactive analytes. By optimizing several parameters, including duty ratio and discharge pressure, we achieved a unique ionization regime where the molecular-related ion [2 M − 3 H]+ was predominantly detected as the base peak with minimal fragmentation. Notably, by reducing the duty ratio from 50% to 5%, both the target ion occupancy and signal intensity were significantly enhanced, achieving a limit of detection (LOD) as low as 0.16 parts per million by volume (ppmv). This sensitivity is several orders of magnitude higher than previously reported thresholds, enabling rapid identification of C4–C6 alkyl nitrite isomers. This method transforms the duty ratio into a powerful diagnostic tool for identifying reactive intermediates, providing a practical and efficient approach for the onsite identification of illegal alkyl nitrites in forensic and security fields.