Determination of rimonabant in human plasma and hair by liquid chromatography-mass spectrometry.
Rimonabant is the first therapeutically relevant cannabinoid antagonist, licensed in Europe for treatment of obesity when a risk factor is associated. The objective of this study was to develop and validate a method for measurement of rimonabant in human plasma and hair using liquid chromatography coupled to mass spectrometry (LC-MS/MS). Rimonabant and AM-251 (internal standard) were extracted from 50 microL of plasma or 10 mg of hair using diethylether. Chromatography was performed on a 150 mm x 2.1 mm C18 column using a mobile phase constituted of formate buffer/acetonitrile. Rimonabant was ionized by electrospray in positive mode, followed by detection with mass spectrometry. Data were collected either in full-scan MS or in full-scan MS/MS mode, selecting the ion m/z 463.1 for rimonabant and m/z 555.1 for IS. The most intense product ion of rimonabant (m/z 380.9) and IS (m/z 472.8) were used for quantification. Calibration curves covered a range from 2.5 (lower limit of quantification) to 1000.0 ng/mL (upper limit of quantification) in plasma and from 2.5 to 1000.0 pg/mg in hair. Validation results demonstrated that rimonabant could be accurately and precisely quantified in both matrixes: accuracy and precision were within 85-115% and within 15% of standard deviation, respectively. Stability studies in plasma showed that rimonabant was stable during the assay procedure, but a 30% decrease was observed for one concentration after 3 weeks at -20 degrees C. This simple and robust LC-MS/MS method can be used for measuring rimonabant concentrations in human plasma and hair either in clinical or in forensic toxicology.
Grassin Delyle
Stanislas
S
Laboratory of Pharmacology-Toxicology, Universitary Hospital Raymond Poincaré, AP-HP, 104 Boulevard Raymond Poincaré, 92380 Garches, France.
Abe
Emuri
E
Devillier
Philippe
P
Alvarez
Jean Claude
JC
D002138:Calibration; D002186:Cannabinoids / Q000037:antagonists & inhibitors*; D002853:Chromatography, Liquid / Q000379:methods*; D006197:Hair / Q000737:chemistry*; D006801:Humans; D010880:Piperidines / Q000032:analysis / Q000097:blood*; D011720:Pyrazoles / Q000032:analysis / Q000097:blood*; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D000077285:Rimonabant; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
D002186:Cannabinoids; D010880:Piperidines; D011720:Pyrazoles; D000077285:Rimonabant