Study of Direct Ionization Mass Spectrometry with a Flared Capillary for Drug Detection

Direct ionization mass spectrometry has the advantages of rapid, in-situ and real-time ionization, which has been widely used for the detection of drugs, explosives, food additives, etc. The coupling between direct ionization source and mass spectrometer vacuum is usually achieved with a narrow baffle hole such as capillary or skimmer, which can result in a significant reduction in the ion transmission efficiency. It is well known that this has become a key bottleneck for the improvement of instrument sensitivity. This study was carried out based on a rapid screening mass spectrometry platform coupled with a pulsed direct current electrospray ionization (pulsed-dc ESI) source, which has the advantages of low sample volume required, high ionization efficiency, no cross-contamination risk, and so on. The instrument performances with flat and flared capillaries under different spray voltages, emitter positions, inner diameters of emitter, diameters of capillary inlet were investigated. For the pulsed-dc ESI emitters with the inner diameter of 5, 20, 50 and 100 μm, the highest ion intensity could be achieved with the 20 μm emitter for all capillaries. Besides, compared with the flat capillary, the ion intensity of flared capillary was more stable to the variation of radial distance between emitter and capillary inlet. By simulating the gas flow and ion trajectories of various capillaries, it was found that the air stream around capillary inlet dominated the ion transmission. For the flat capillary, the gas flow pointed inward only in the area of very close to the porthole. As a contrast, the gas velocities of flared capillaries increased gradually from the entrance of conical mouth to the narrowest part of capillary, of which the directions always pointed to the capillary’s porthole. Due to the larger radial focusable airflow area, the flared capillaries, especially the flared capillary with an inlet diameter of 6 mm could evidently improve the ion transmission efficiency between the direct ionization source and the mass spectrometer. In the simulation, the enhancement of ion transmission efficiencies by fared capillaries was more prominent for high mass-to-charge ratio ions, of which the motion usually was more sensitive to gas flow because of lower mobility. Compared to the conventional flat capillary, the ion signal intensity of 10 μg/L standard methamphetamine solution by the flared capillary of 6 mm in the inlet diameter had increased 3.3 times. The signal-to-noise ratios of five conventional drugs, such as methamphetamine, 3,4-methylenedioxymethamphetamine, ketamine, cocaine, and O₆-monoacetylmorphine in hair matrix were also boosted to certain degrees. Especially for ketamine, the signal-to-noise ratio of the flared capillary to the flat capillary was up to 3.3. The results showed that the adoption of a flared capillary can significantly increase the detection sensitivity of direct ionization screening platform, which does not require any complex modification to the instrument.