Sensitive determination of THC and main metabolites in human plasma by means of microextraction in packed sorbent and gas chromatography-tandem mass spectrometry

Cannabis is one of the most available and consumed illicit drug in the world and its identification and quantification in biological specimens can be a challenge given its low concentrations in body fluids. The present work describes a fast and fully validated procedure for the simultaneous detection and quantification of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and its two main metabolites 11-hydroxy Delta(9)-tetrahydrocannabinol (I1-OH-THC) and 11-nor-9-carboxy-Delta(9)- tetrahydrocannbinol (THC-COOH) in plasma samples using microextraction by packed sorbent (MEPS) and gas chromatography-tandem mass spectrometry (GC-MS/MS). A small plasma volume (0.25 mL) pre-diluted (1:20), was extracted with MEPS Ml sorbent as follows: conditioning (4 cycles of 250 mu L methanol and 4 cycles of 250 mu L 0.1% formic acid in water); sample load (26 cycles of 250 mu L); wash (100 mu L of 3% acetic acid in water followed by 100 mu L 5% methanol in water); and elution (6 cycles of 100 mu L of 10% ammonium hydroxide in methanol). The procedure allowed the quantification of all analytes in the range of 0.1-30 ngimL. Recoveries ranged from 53 to 78% (THC), 57 to 66% (11-OH-THC) and 62 to 65% (THC-COOH), allowing the limits of detection and quantification to be set at 0.1 ng/mL for all compounds. Intra-day precision and accuracy revealed coefficients of variation (CVs) lower than 10% at the studied concentrations, with a mean relative error within +/- 9%, while inter-day precision and accuracy showed CVs lower than 15% for all analytes at the tested concentrations, with an inaccuracy within +/- 8%. (C) 2016 Elsevier B.V. All rights reserved.