Gas-chromatographic determination of nanogram amounts of enantiomers of nortilidine, a main metabolite of tilidine, in biological specimens.

We report a specific and sensitive method for determination of the individual optical isomers of nortilidine, a main metabolite of tilidine, with the aid of a nitrogen-sensitive detector. With N-trifluoroacetyl-L-leucyl chloride as chiral reagent, the diastereomeric derivatives of the nortilidine enantiomers could be separated and quantified in the nanogram range. Under these conditions, the enantiomers of bisnortilidine, another main metabolite of tilidine, were also separated. Investigations in rats with the enantiomers of tilidine and nortilidine indicated that no racemization occurs during N-demethylation in the organism. After oral and intravenous administration of 50 mg of tilidine.HCI to a human volunteer, identical concentrations of nortilidine enantiomers were found in the plasma.