Photothermal Desorption and Reagent-Assisted Low-Temperature Plasma Ionization Miniature IT-MS/MS for On-Site Analysis of Illicit Drugs in Saliva and Urine

Globally, drug-impaired driving fatalities now exceed those from drunk driving, urging the need for on-site and roadside detection methods. In this study, a photothermal desorption and reagent-assisted low-temperature plasma ionization miniature ion trap mass spectrometer (PDRA-LTP-ITMS) was developed for on-site detection of drug-impaired driving. The pseudomultiple reaction monitoring (MRM) in PDRA-LTP-ITMS enables continuous ion selection during ion introduction and improved sensitivity to nearly 3-fold compared with the conventional full scan mode. The PDRA-LTP integrated the ionization source and photothermal desorption region into the LTP tube with a volume of 0.05 mL. Photoionization and Penning ionization from LTP discharging facilitate proton transfer reactions with the dopant and produce characteristic [M + H] + for drugs. Dopants of butanol and acetone were separately employed to enhance the thermal desorption and ionization efficiency, resulting in a 2.6-fold sensitivity increase. Saliva and urine samples were collected with a medical swab, and only 10 μL of sample is required for each analysis. The sample is rapidly heated to 250 °C using a halogen lamp and analyzed within 5 s. With these designs, a 4-fold and 10-fold increase in sensitivity was achieved compared to APPI and nano-ESI, respectively. The limits of detection (S/N = 3) of illicit drugs, including MDMA, MDA, methamphetamine, amphetamine, ketamine, and cocaine, in saliva ranged from 4.5 pg μL –1 to 20 pg μL –1 and met the threshold values of GA1333–2017. The performance of the PDRA-LTP-ITMS was even comparable to that of LTQ-Orbitrap Velos Pro ETD MS, providing a novel method of rapid on-site drug-impaired driving analysis.