Quantitative determination of five cannabinoids in blood and urine by gas chromatography tandem mass spectrometry applying automated on‐line solid phase extraction

Cannabis is the most frequently consumed illegal substance worldwide. More recently, an increasing number of legal cannabis products low in psychoactive Δ(9)‐tetrahydrocannabinol (THC) but high in non‐intoxicating cannabidiol (CBD) are being more widely consumed. While the detection and quantification of THC and its metabolites in biological matrices is an important forensic‐toxicological task, additional detection of CBD is also important, for example, when examining the plausibility of consumer's statements. This report describes the method validation for the quantitative determination of THC and its two major metabolites, 11‐hydroxy‐THC (OH‐THC) and 11‐nor‐9‐carboxy‐THC (THC‐COOH), as well as CBD and cannabinol (CBN) in whole blood and urine. The method employs automated on‐line solid phase extraction coupled to gas chromatography tandem mass spectrometry (GC–MS/MS). The method was fully validated according to guidelines of the Swiss Society of Legal Medicine (SGRM) and the Society of Toxicological and Forensic Chemistry (GTFCh). The method fulfilled the validation criteria regarding analytical limits, accuracy and precision, extraction efficacy, and sample stability. The limits of detection (LODs) in whole blood and urine were 0.15 ng/mL for THC, OH‐THC and CBD, 0.1 ng/mL for CBN, and 1.0 ng/mL for THC‐COOH. The limits of quantification (LOQ) in whole blood and urine were 0.3 ng/mL for THC, OH‐THC and CBD, 0.2 ng/mL for CBN, and 3.0 ng/mL for THC‐COOH. The fully validated and automated method allows sensitive and robust measurement of cannabinoids in whole blood and urine. Detection of CBD provides additional information regarding consumed products.