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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.

Doxepin is a tricyclic antidepressant marketed as an irrational mixture of cis- and trans-geometric isomers in the ratio of 15:85. A convenient high-performance liquid chromatographic (HPLC) procedure for simultaneous quantitation of geometric isomers of doxepin and N-desmethyldoxepin in plasma and urine is described. The HPLC procedure employed a normal phase system with a silica column and a mobile phase consisting of hexane-methanol-nonylamine (95:5:0.3, v/v/v), a UV detector and nortriptyline as the internal standard. The liquid-liquid extraction solvent was a mixture of n-pentane-isopropanol (95:5, v/v). The limit of quantitation was 1 ng/ml for each isomer. The calibration curves were linear over the ranges 1-200 ng/ml (plasma) and 1-400 ng/ml (urine). In plasma, the accuracy (mean +/- S.D.) (97.53 +/- 1.67%) and precision (3.89 +/- 1.65%) data for trans-doxepin were similar to corresponding values for urine, i.e., 97.10 +/- 2.40 and 3.82 +/- 1.14%. Accuracy and precision data for trans-N-desmethyldoxepin in plasma were 97.57 +/- 2.06 and 4.38 +/- 3.24%, and in urine were 97.64 +/- 3.32 and 5.26 +/- 1.83%, respectively. Stability tests under three different conditions of storage indicated no evidence of degradation. The recovery of doxepin was 61-64% from plasma and 63-68% from urine. The method has been applied to analyses of plasma and urine samples from human volunteers and animals dosed with doxepin.