Simultaneous quantification of cannabinoids tetrahydrocannabinol, cannabidiol and CB1 receptor antagonist in rat plasma An application to characterize pharmacokinetics after passive cannabis smoke inhalation and co-administration of rimonabant.
A highly sensitive and selective liquid chromatography-tandem mass spectrometry method for the determination of tetrahydrocannabinol (THC), cannabidiol, and rimonabant in rat plasma was developed. Analytes and the internal standard were extracted from plasma using a combination of protein precipitation followed by liquid-liquid extraction. Chromatographic separation was done using Waters Symmetry C18, 4.6 × 150 mm, 5 um column using 10 mm ammonium formate buffer and methanol. The total run time was 6 min, and separation was achieved using isocratic elution at a flow rate of 1 mLmin using a 1090 (aqueous organic) ratio. The ionization of the analytes was optimized using electrospray ionization in positive mode, and multiple reaction mode was used for this analysis. This method showed linearity from 0.1 to 100 ngml for all the analytes and was validated according to FDA Bioanalytical Method Validation Guidance in terms of accuracy, precession, linearity, stability, matrix effect, recovery, and stability. This method was successfully applied to characterize the pharmacokinetics of THC in rats after continuous passive smoke exposure for 50 min when rimonabant was co-administered with cannabis smoke. Maximum concentration (C