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.