An Efficient, Robust Method for the Determination of Cannabinoids in Whole Blood by LC-MS-MS

Due to the high prevalence of cannabinoids in forensic toxicology casework, it is desirable to have an efficient method that uses a small volume of blood and requires a minimal sample preparation. Although many methods have been reported, they are often labor intensive, require special sample preparation materials, use 1 mL or more of specimen or are difficult to replicate. The liquid chromatography with tandem mass spectrometry (LC-MS-MS) method presented herein employs a rapid and simple liquid-liquid extraction, has been successfully applied in two different laboratories, uses 0.5 mL of specimen and was extensively validated. The validated limit of detection and limit of quantitation were 1 ng/mL for delta-9-tetrahydrocannabinol (THC) and 11-hydroxy-delta-9-tetrahydrocannabinol (OH-THC) and 5 ng/mL for 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THCA). Each analyte demonstrated a zero-order linear range (r² > 0.990) with 1/x weighting of 1-40 ng/mL for THC and OH-THC and 5-200 ng/mL for THCA. The coefficient of variation of replicate analyses was within 14%. Bias was within ±13% of the prepared concentration. The validated method provides a sensitive, efficient and robust procedure for the quantitation of cannabinoids in blood using LC-MS-MS and a sample volume of 0.5 mL.