Continuous atmospheric pressure interfaced ion trap mass spectrometry with thermal desorption for detection of nonvolatile drugs.

The escalating need for prompt and highly sensitive on-site detection of trace-level drugs is fueling the advancement of miniature, high-performance mass spectrometers and analytical methodologies. In this study, a miniature continuous atmospheric pressure interfaced ion trap mass spectrometer integrated with thermal desorption acetone-assisted photoionization (TD-CAPI-ITMS) was developed for highly sensitive detection of nonvolatile drugs in saliva and blood. By strategically extending the sampling time of the TD-CAPI-ITMS to cover the entire desorption process, a remarkable two-order-of-magnitude enhancement in the signal intensity of individual drugs was observed. Moreover, the simultaneous detection of drug mixtures with widely varying boiling points and saturation vapor pressures was accomplished. Optimization of the parameters yielded a limit of detection (LOD) for ketamine and 5F-EMB-PICA of 1 pg/μL accompanied by a robust stability, as evidenced by a relative standard deviation (RSD) of 5.30 %. Combined with straightforward liquid-liquid extraction, the sensitivity of drugs in saliva as low as 10 pg/μL was achieved, which met the requirements of Chinese national standard GA1333-2017. Owing to its exceptional sensitivity, the matrix effect present in blood samples was significantly alleviated through dilution, allowing for accurate monitoring of antibiotic concentrations. The results underscore the substantial potential of the TD-CAPI-ITMS for lab-free applications in drug-related forensic analysis, therapeutic drug monitoring, and pharmacokinetic studies.