TY - JOUR
T1 - Quantification of rimonabant (SR 141716A) in monkey plasma using HPLC with UV detection
AU - Javors, Martin A.
AU - Sanchez, Jesus J.
AU - McMahon, Lance R.
N1 - Funding Information:
This work was supported by USPHS grant DA19222.
PY - 2010/7
Y1 - 2010/7
N2 - 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 CB1 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, C18 column (4.6 mm i.d. × 150 mm length, 5 μm), 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 (r2 = 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.
AB - 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 CB1 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, C18 column (4.6 mm i.d. × 150 mm length, 5 μm), 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 (r2 = 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.
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U2 - 10.1093/chromsci/48.6.491
DO - 10.1093/chromsci/48.6.491
M3 - Article
C2 - 20822666
AN - SCOPUS:77955483121
VL - 48
SP - 491
EP - 495
JO - Journal of Chromatographic Science
JF - Journal of Chromatographic Science
SN - 0021-9665
IS - 6
ER -