Determination of cyproheptadine in plasma and urine by GLC with a nitrogen-sensitive detector.

A method for the determination of cyproheptadine in plasma and urine was developed using the N -ethyl homologue as an internal standard. After extraction of the drug from an alkalinized sample into petroleum ether-isoamyl alcohol, back-extraction into 0.1 N HCl, washing the aqueous phase with fresh solvent, re-extraction into petroleum ether after alkalinization, the solvent was evaporated. The reconstituted residue was analyzed by GLC using a SP-2250 column and nitrogen-sensitive detector. Concentrations as low as 3 ng/ml could be determined. Plots of peak area of cyproheptadine-peak area of internal standard versus cyproheptadine concentration were linear over the range studied with correlation coefficients of 0.9945 and 0.9924 for plasma and urine, respectively. The method was used to determine the peak time (0.5 hr), peak concentration (33 ng/ml average), and apparent half-life (3 hr) in two dogs after oral administration of 1 mg of cyproheptadine/kg.

GLC determination of (-)-1-cyclopropylmethyl-4-(3-trifluoromethylthio-5H-dibenzo [a,d]cyclohepten-5-ylidene)piperidine in human plasma and urine.

(-)-1-Cyclopropylmethyl-4-(3-trifluoromethylthio-5H-dibenzo [a,d]cyclohepten-5-ylidene)piperidine (MK-160) was extracted from human plasma and urine with petroleum ether and quantitated by GLC using a nitrogen-sensitive detector. A homologue of the drug served as the internal standard. The method is specific for the drug in the presence of potential metabolites and is capable of measuring concentrations in plasma as low as 6 ng/ml.

Disposition and metabolism of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine in rats, dogs, and monkeys.

The disposition and metabolism of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), a new agent with potent anticonvulsant, central sympathomimetic, and apparent anxiolytic properties, was studied in rats, dogs, and rhesus monkeys. [3H]benzene-MK-801 was administered orally at a dose of 1 mg/kg. MK-801 was measured in plasma by GLC using a nitrogen detector; the overall sensitivity of the method was 3 ng/ml. Radioactivity was excreted mainly in urine of dogs and monkeys but fecal excretion in rats was also extensive. The apparent plasma t1/2 of MK-801 in the rat and dog was approximately 1 hr. Maximal plasma levels of MK-801 in the rat, dog, and monkey were 46 (0.5 hr), 16 (0.25 hr), and 10 (2 hr) ng/ml, respectively. Radioactivity was extensively excreted in rat bile and was widely distributed among various tissues. Major metabolites of the drug in rat and dog urine were the 2- and 8-hydroxy analogs (rat) and the N-hydroxy derivative (dog).