Identification and determination of propafenone and its principal metabolites in human urine using capillary gas chromatography/mass spectrometry

The capillary gas chromatography/mass spectrometry of trimethylsilyl‐trifluoroacetyl, trifluoroacetyl and penta‐fluoropropionyl (PFP) derivatives of the antiarrhythmic agent propafenone (Rytmonorm ® ), as well as its main metabolites N ‐despropyl‐propafenone and 5‐hydroxy‐propafenone, have been investigated. Both electron impact and positive isobutane chemical ionization mass spectrometry using the Ion Trap Detector ® have been evaluated. The presence of propafenone and its co‐extracted metabolites in human urine at time intervals after the oral administration of 150 mg Rytmonorm ® to healthy volunteers was established, and the urinary excretion of propafenone and 5‐hydroxy‐propafenone was calculated using selective chemical ionization mass spectrometric detection. Only a few per cent of the dose was excreted unchanged in the urine. Large intersubject variabilities had been observed also. The large dynamic range of the Ion Trap Detector ® and the high correlation coefficients (0.92–0.99) of the calibration curves were striking.