The pharmacokinetic analysis is performed in a three-step procedure: sample extraction, sample purification by thin layer chromatography (TLC) and quantitative sample detection by time-of-flight (TOF) mass spectrometry. 252Cf plasma desorption (PD) mass spectrometry utilizing the fission fragment-induced ionization and desorption of non-volatile compounds is suitable as a universal, non-destructive detector in TLC. Here TLC and mass spectrometry are operated in an off-line combination. As an example some pharmacokinetic data for etoposide (VP 16-213) together with calibration data are presented. The new experimental method is discussed in terms of sensitivity and detection limit.

Drug monitoring is performed by means of sample extraction, sample purification by high-performance liquid chromatography (HPLC), and sample detection by time-of-flight mass spectrometry. This mass spectrometry utilizing 252Cf fission fragment-induced ionization and desorption of nonvolatile compounds is suitable as a universal, nondestructive detector in HPLC. Liquid chromatography and mass spectrometry are combined, so that mass analysis can be operated online and offline to the fractional sampling of the effluent and the samples can still be recovered. As an alternative to HPLC separation, samples can be purified by thin-layer chromatography (TLC), resulting an offline TLC + MS combination. Preliminary pharmacokinetic data for etoposide (VP16-213) together with calibration data are presented, and are discussed with reference to the sensitivity and detection limit of the new experimental method.

A ='Cf plasma desorption mass spectrometer has been set up to anaiyse thin layers of non-volatile organic samples. Molecular and fragment ions were produced and their mass was determined by a time-of-flight measurement. A novel interface combines a high-performance liquid chromatograph with the =*Cf plasma desorption mass spectrometer in a twofold way: introducing the effluent continuously thromgb a capillary inlet in the on-line liqUia chromatography mass spectrometry mode or transferring already prepared samples through a vacuum lock into the mass spectrometer in the off-line liquid chromatography+mass spectrometry mode. The off-line mode has been applied for the quantitative analysis of phannaceutid in blood using stable isotope labelled standards. INTRODUCTIONThis study stems from interdisciplinary collaboration between physical chemistry and clinical medicine at our university with the aim of investigating the bioavailability and kinetics of antiarrhythmic drugs (used in cardiology). Most of these drugs produce plasma concentrations which vary greatly from patient to patient and even from time to time. Some have a high first pass metabolism (in the liver) after oral dosage and this seems to be one possible source of variation. It is desirable to monitor the quality of dosage forms as well as concentrations of active drug and metabolites in biological fluids (plasma, saliva, urine). A sensitivity in the order of 1 n g~m -~ is needed for such a quantitative analysis.The capabilities of a high-performance liquid chromatography (HPLC) in the quantitative analysis of pharmaceuticals in blood are generally recognized.' However, in many cases this analytical method produces doubtful results due to the narrow selectivity of detectors commonly used with HPLC, e.g. ultraviolet (W) absorption, fluorescence, refraction, conductivity and electrochemical detectors. Operating a highperformance liquid chromatograph with a mass spectrometer as a universal detector should overcome many of these problems.2 The versatility and sensitivity of liquid chromatography mass spectrometry (LC/MS)24 should be comparable with the powerful gas chromatography mass spectrometry (GC/MS) method.Mass spectrometry alone can be applied very successfully for quantitative analysis in biochemistry and medicine,' especially when stable isotope labelled f Author to whom correspondence should be addressed.drugs are added as internal standards?.' Generally, mass spectra are greatly dependent upon the ionization method. Field desorption and several surface ionization methods, such as secondary ion mass spectrometry (SIMS), laser induced mass spectrometry (LIMS) and ' "Cf plasma desorption mass spectrometry (PDMS) have one common advantage:' they can be used to produce and detect molecular ions of fragile samples, i.e. molecules which are thermally unstable and/or have a low vapour pressure. Thus, a mass spectrometer which utilizes one of these ionization methods should be an ideal detector for HPLC. Since none of the commercially available liquid chrom...

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