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.