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The use of several mass spectrometry technologies including electron impact (EI) and positive chemical ionization (CI) in both full-scan and multiple ion detection (MID) analysis for the urine analysis of several beta blockers and metabolites has been investigated. These drugs were extracted using an alkaline solid-phase extraction procedure and identified as their respective trimethylsilyl-trifluoroacetyl (TMS-TFA) derivatives on capillary gas chromatography/mass spectrometry. Isobutane proved to be the preferred reagent gas for the positive CI mass spectrometry of TMS-TFA derivatives of beta blockers, in comparison with others, such as methanol, ammonia and methane, since mass spectra with little fragmentation and abundant ions at high mass were obtained. By combining EI mass spectrometry and isobutane positive CI mass spectrometry using the ion trap detector, the identities of the main co-extracted metabolites were confirmed. Absolute detection limits were 0.15 ng for full-scan analysis (EI as well as positive CI mass spectrometry) and 0.08 ng for MID analysis (EI as well as CI mass spectrometry). The detection times of beta blockers in human urine were at least two- to three-fold the elimination half-life of these drugs. The analytical potential of the above mass spectrometric techniques has been discussed.

The capillary gas chromatography/mass spectrometry of trimethylsilyl-trifluoroacetyl, trifluoroacetyl and pentafluoropropionyl (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.

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