Drug overdoses in the country have risen dramatically in recent years, and many cases can be attributed to synthetic drugs such as fentanyl, its analogs, and other opioids. The synthetic drug market is ever changing, and traditional screening methods lack the ability to detect newly emerging substances. Paper spray ionization is an ambient ionization technique with a wide versatility in both analyte variety and applications. Common uses for paper spray have been in clinical, environmental, national security, and forensics analysis. This is attributed to the ability to analyze crude biofluid samples rapidly and efficiently. For synthetic drug screening, the number of drug targets is large and capricious. Non-targeted mass spectrometry data acquisition methods, both data dependent and independent, could therefore be useful. Most research into these data acquisition techniques have been utilized with liquid chromatography mass spectrometry. In this study, we compare the sensitivity and specificity of three different MS data acquisition methods in paper spray MS screening of synthetic drugs in plasma. The data acquisition methods to be compared are data dependent acquisition, sequential window acquisition of all theoretical mass spectra (SWATH), and targeted MS/MS acquisition using parallel reaction monitoring (PRM). It is expected that the SWATH data acquisition method will have better sensitivity than DDA, but with a higher false positive rate. PRM will likely have the best sensitivity and the lowest incidence of false positives but has a smaller compound coverage being limited to specified MS/MS scans only. The magnitude of the tradeoffs in sensitivity and specificity will be defined for 20 different synthetic drugs in the opioid, stimulant, benzodiazepine, synthetic cannabinoid, and dissociative classes.

Sequential windowed acquisition of all theoretical mass (SWATH) vs data dependent acquisition (DDA) vs parallel reaction monitoring (PRM) acquisition comparison of newly emerging psychoactive substances in plasma by paper spray mass spectrometry

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