A direct mass spectrometry method for cannabinoid quantitation in urine and oral fluid utilizing reactive paper spray ionization

Abstract

A direct mass spectrometry method utilizing reactive paper spray ionization was developed for sensitive cannabinoid quantitation in biofluid matrices. The ca. 2-minute sample measurements used on-paper derivatization to significantly increase paper spray mass spectrometry (PS-MS) positive ion mode sensitivity while minimizing sample preparation steps. Calibrations demonstrate high linearity, with R² > 0.99 for (−)-trans-Δ⁹-tetrahydrocannabinol (THC) in oral fluid and 11-nor-9-carboxy-Δ⁹-tetrahydrocannabinol (THC-COOH) in urine. The limit of detection and lower limit of quantitation were 0.78 and 10 ng mL⁻¹ for THC in oral fluid and 1.3 and 10 ng mL⁻¹ for THC-COOH in urine, respectively. THC-COOH levels measured by reactive PS-MS in seven spiked human urine samples showed bias of −9.4 to 5.9%, and percent difference values of −16.8 to 9.8% in comparison with a reference LC-MS method. Based upon the method simplicity, validation experiments, sensitivity, and rapidity, we conclude that reactive PS-MS has potential applications for rapid cannabinoid drug testing in urine and oral fluid.