Quantification of rimonabant (SR 141716A) in monkey plasma using HPLC with UV detection.
Using an isocratic high-performance liquid chromatography (HPLC) system and UV detection, a simple and precise analytical procedure was developed to quantify levels of the CB(1) receptor antagonist rimonabant in the plasma of rhesus monkeys. Rimonabant was extracted from plasma samples into 5% isopropanol in hexane. After separation, the isopropanol-hexane fractions were dried to residue, redissolved in mobile phase, and then injected into the HPLC. The HPLC system included an acetonitrile-phosphate buffer (62:38, v/v) mobile phase (pH 6.7), flow rate of 1.5 mL/min, C(18) column (4.6 mm i.d. x 150 mm length, 5 microm), and UV detection at 280 nm. Retention times for rimonabant and doxepin (internal standard) were 9.9 and 2.4 min, respectively. The regression of the spiked calibrator curve was linear from 60 to 4000 ng/mL (r(2) = 0.996). The lower limit of quantification was 60 ng/mL, and recovery was 83.6%. Rimonabant was stable in stock solutions and monkey plasma across a range of temperatures and concentrations. To demonstrate utility, plasma rimonabant was measured in six rhesus monkeys at 60 and 240 min after intramuscular administration of 1 mg/kg rimonabant. Rimonabant levels ranged from 175 to 1290 ng/mL. The analytical assay described here provides a simple and accurate procedure for multiple within-subject measurements of the CB(1) antagonist rimonabant.
Javors
Martin A
MA
Department of Psychiatry, University of Texas Health Science Center, San Antonio, Texas, USA. javors@uthscsa.edu
Sanchez
Jesus J
JJ
McMahon
Lance R
LR
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004316:Doxepin / Q000032:analysis / Q000737:chemistry; D005260:Female; D016014:Linear Models; D008253:Macaca mulatta / Q000097:blood*; D008297:Male; D010880:Piperidines / Q000097:blood* / Q000737:chemistry; D011720:Pyrazoles / Q000097:blood* / Q000737:chemistry; D015203:Reproducibility of Results; D000077285:Rimonabant; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
D010880:Piperidines; D011720:Pyrazoles; D004316:Doxepin; D000077285:Rimonabant
J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Mar 1;863(2):258-65
18258497
Psychopharmacology (Berl). 2001 Aug;156(4):369-80
11498713
Behav Pharmacol. 2005 Sep;16(5-6):275-96
16148435
Anal Chem. 2007 Aug 1;79(15):5668-73
17605466
Life Sci. 1995;56(23-24):1941-7
7776817
Arch Gen Psychiatry. 2001 Apr;58(4):322-8
11296091
FEBS Lett. 1994 Aug 22;350(2-3):240-4
8070571
Psychopharmacology (Berl). 2006 Oct;188(3):306-14
16953389
Nat Neurosci. 2000 Nov;3(11):1073-4
11036260
Drug Metab Dispos. 2005 Apr;33(4):508-17
15616153
Psychopharmacology (Berl). 2007 May;192(1):135-45
17245585