Sensitive screening of synthetic cannabinoids using liquid chromatography quadrupole time-of-flight mass spectrometry after solid phase extraction

Analysis of synthetic cannabinoids still poses a challenge for many institutions due to the number of available substances and the constantly changing drug market. Both new and well-known substances keep appearing and disappearing on the market, making it hard to adapt analytical methods in a timely manner. In this study, we developed a qualitative screening approach for synthetic cannabinoids and their metabolites by means of liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Samples were measured in data-dependent auto-MS/MS mode and identified by fragment spectra, retention time and accurate mass. Two established solid phase extractions were compared using fortified serum and urine samples. Mixes of 199 synthetic cannabinoids and 110 metabolites were used in 1- and 10-ng/ml concentrations. Up to 93% of synthetic cannabinoids and 74% of metabolites were detected in fortified 1-ng/ml samples. From February 2018 to October 2020, we analyzed 1492 cases, of which 73 cases were positive for synthetic cannabinoids or metabolites. 5F-MDMB-PICA, 4F-MDMB-BINACA, MDMB-4en-PINACA, and 4F-MDMB-BICA were most frequently detected. Hydrolysis metabolites were detected in many blood samples, providing a longer detection window. Quantification was conducted via liquid chromatography triple quadrupole mass spectrometry after liquid-liquid extraction. Concentrations were mostly close to 1 ng/ml in blood samples. LC-QTOF-MS was able to detect substances above trace quantities (< 0.1 ng/ml) in most cases, therefore fulfilling its purpose as a sensitive general screening approach. Expansion of the screening library was uncomplicated and enables future additions for up to thousands of targets.

Automated summary

A qualitative screening approach using LC-QTOF-MS was developed for synthetic cannabinoids and their metabolites, able to detect trace quantities of most substances accurately. Hydrolysis metabolites were found in blood samples, extending the detection window.