Semiquantitative Activity-Based Detection of JWH-018, a Synthetic Cannabinoid Receptor Agonist, in Oral Fluid after Vaping Annelies Cannaert, Maria del Mar Ramírez Ferna ́ ndez, Eef L. Theunissen, Johannes G. Ramaekers, Sarah M. R. Wille, and Christophe P. Stove* Cite This: Anal. Chem. 2020, 92, 6065-6071 Read Online ACCESS Metrics & More Article Recommendations ABSTRACT: The rapid proliferation of new synthetic cannabinoid receptor agonists (SCRAs) has initiated considerable interest in the development of so-called “untargeted” screening strategies. One of these new screening technologies involves the activity-based detection of SCRAs. In this study, we evaluated whether (synthetic) cannabinoid activity can be detected in oral fluid (OF) and, if so, whether it correlates with SCRA concentrations. OF was collected at several time points in a placebo-controlled JWH-018 administration study. The outcome of the cell-based cannabinoid reporter system, which monitored the cannabinoid receptor activation, was compared to the quantitative data for JWH-018, obtained via a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. A total of 175 OF samples were collected and analyzed via both methods. The cannabinoid reporter assay correctly classified the vast majority of the samples as either negative (<0.25 ng/mL; 74/75 = 99%) or having low (0.25-1.5 ng/mL; 16/16 = 100% and 1.5-10 ng/mL; 37/41 = 90%), mid (10-100 ng/mL; 23/25 = 92%) or high (>100 ng/mL; 16/18 = 89%) JWH-018 concentrations. Passing-Bablok regression analysis yielded a good linear correlation, with no proportional difference between both methods (slope 0.97; 95% confidence interval 0.86-1.14) and only a small systematic difference. This is the first study to demonstrate the applicability of an untargeted, activity-based approach for SCRA detection in OF. Additionally, the outcome of the cannabinoid reporter assay was compared to the gold standard (LC-MS/MS), showing a good correlation between both methods, indicating that the cannabinoid reporter assay can be used for an estimation of drug concentrations. B y the end of 2019, 950 novel substances were reported to the United Nations Office on Drugs and Crime (UNODC) Early Warning Advisory on new psychoactive substances (NPS) by governments, laboratories, and partner organizations. These substances include a broad range of drugs, such as synthetic cannabinoid receptor agonists (SCRAs), stimulants, opioids, and benzodiazepines. 1 The rise of NPS has put a huge strain on drug legislations and clinical and forensic laboratories worldwide in terms of legality and detectability. Several (new) technologies have been developed to cope with the problem of detection of NPS. One of these new screening technologies uses an untargeted approach and involves the activity-based detection of SCRAs and synthetic opioids in several biological matrices, including urine, serum, plasma, and vitreous. 2-6 In many cases though, for example, in the context of driving under the influence of drugs, workplace testing, or in drug abstinence monitoring, oral fluid (OF) is used as a matrix for the analysis of drugs of abuse. 7-10 OF offers the advantage that the sampling is noninvasive and that the parent compounds can be detected in the matrix. This study is the first to assess whether (synthetic) cannabinoid activity can be detected in OF. To evaluate the proof-of- Received: February 3, 2020 Accepted: March 22, 2020 Published: March 22, 2020 Article pubs.acs.org/ac © 2020 American Chemical Society 6065 https://dx.doi.org/10.1021/acs.analchem.0c00484 Anal. Chem. 2020, 92, 6065-6071 Downloaded via UNIV GENT on May 12, 2020 at 12:52:02 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles. brought to you by CORE View metadata, citation and similar papers at core.ac.uk provided by Ghent University Academic Bibliography