Liquid chromatographic–mass spectrometric quantitation of Δ9-tetrahydrocannabinol and two metabolites in pharmacokinetic study plasma samples

A sensitive method for the determination of Δ9-tetrahydrocannabinol and its metabolites, 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid and 11-hydroxy-Δ9-tetrahydrocannabinol, in rat and guinea pig plasma was developed using high-performance liquid chromatographic separation with electrospray ionization mass spectrometry detection and a simple liquid–liquid extraction technique. The mean recoveries for Δ9-tetrahydrocannabinol, 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid, and 11-hydroxy-Δ9-tetrahydrocannabinol were 96, 92, and 85%, respectively. The lower limit of quantification (LLOQ) for all three compounds was 5 ng/ml and the limit of detection (LOD) was 2 ng/ml. This assay method utilizes the increased sensitivity and selectivity of mass spectrometric (MS) detection and a simple extraction step for the determination of Δ9-tetrahydrocannabinol and its metabolites in plasma, and thus yields a more efficient pharmacokinetic analysis method than has previously been described.