Simple protein precipitation-based analysis of Δ9-tetrahydrocannabinol and its metabolites in human serum by liquid chromatography–tandem mass spectrometry

A liquid chromatography–tandem mass spectrometry (LC–MS/MS) quantification method based on a direct protein precipitation with the mobile phase was developed, validated and applied for the analysis of Δ9-tetrahydrocannabinol (THC), 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) in human serum for forensic purposes. Chromatographic separation was performed with a Luna 5 µm C18 (2) 100 A, 150 × 2 mm analytical column and the elution with a programmed flow of a mobile phase consisting of A (H2O/methanol, 95:5, v/v) and B (H2O/methanol, 3:97, v/v), both with 10 mM ammonium acetate and 0.1 % acetic acid. The results of the validation experiments demonstrated that the strategy presented can be applied successfully for a fast, simple and cost effective LC–MS/MS analysis of THC and its metabolites. A potential conversion of THC-COOH glucuronide to THC-COOH during sample preparation/analysis could be excluded.