Determination of endocannabinoid receptor antagonist SR141716 (rimonabant) in plasma by liquid chromatograph tandem mass spectrometry.
SR141716 (rimonabant) is an endocannabinoid receptor antagonist. Endocannabinoids are a class of chemicals that affect neurotransmission via G-protein coupled CB1 (brain) and CB2 (peripheral tissue) receptors. Numerous animal studies have shown that SR141716 binds with the CB1 receptor in the brain, resulting in several biological consequences including reduced alcohol intake and reward as well as reduced food consumption. In this work, an analytical method based on liquid chromatography and electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) has been developed and validated for the quantitative measurement of SR141716 in both human and rat plasma to support the investigation of this compound. A suitable internal standard (AM251) has been chosen and the experimental conditions have been optimized for the separation and detection of singly charged positive ions of SR141716 and the internal standard. A protein precipitation protocol has been developed for extraction of SR141716 and the internal standard from plasma samples. Quantitation was achieved using multiple-reaction-monitoring (MRM) mode for SR141716 (m/z 463-->m/z 363) and the internal standard (m/z 555-->m/z 455) and calibration curve over the concentration range of 5.00-1000 ng/ml was plotted using the peak-area ratio versus the concentration of SR141716 with a LOD and LLOQ of 1.09 and 3.62 ng/ml, respectively. The method developed has been used to analyze SR141716 in rat plasma samples from an animal study.
McCulloch
Melissa
M
Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115-2214, USA.
Zhou
Xiang
X
Xu
Yan
Y
Brunell
Steve
S
Spear
Linda
L
D000818:Animals; D019540:Area Under Curve; D002138:Calibration; D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators / Q000097:blood*; D005591:Chemical Fractionation / Q000295:instrumentation; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D063388:Endocannabinoids; D005240:Feasibility Studies; D006801:Humans; D010880:Piperidines / Q000097:blood*; D011720:Pyrazoles / Q000097:blood*; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid / Q000378:metabolism; D012015:Reference Standards; D000077285:Rimonabant; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; C103505:AM 251; D000077285:Rimonabant