Miniaturized automated matrix solid-phase dispersion extraction of pesticides in fruit followed by gas chromatographic-mass spectrometric analysis.

In this study a simple and fast miniaturized automated matrix solid-phase dispersion method for the sample preparation and quantitative extraction of pesticides was developed and evaluated. Only 25 mg of sample and 100 microl of organic solvent were used per analysis for this new miniaturized set-up. The extracts were subsequently analysed by GC-MS without any further purification. The method was optimized for oranges and tested for the determination of a variety of organophosphorus pesticides and a pyrethroid at concentration levels below the maximum residue levels set by the European Union and authorities in The Netherlands. The limits of detection were 4-90 microg/kg. The recoveries for pesticides in orange were 83-118% and the relative standard deviations for the total procedure were 10-13% (n=4) at the limit of quantification. The feasibility of the developed method for apple, pear and grapes was also studied. Equally good results were obtained, but for apple the washing step should be omitted.

Pharmacokinetics and metabolism of the staurosporine analogue CGP 41 251 in mice.

Studies with CGP 41 251 (I), an N-benzoylstaurosporine derivative and PKC-alpha inhibitor, revealed that oral administration of 400 microg/day of the compound to wild type mice on four successive days reversed multi drug resistance (Killion et al. Oncology Research 7: 453-459, 1995). In our study, the same regimen of administration was followed with the primary objective to establish the pharmacokinetics and metabolism of the compound and to substantiate at which plasma concentrations of CGP 41 251 multi drug resistance (MDR) reversal can be expected. Concentrations of CGP 41 251 and metabolites in plasma were determined by a validated high performance liquid chromatography (HPLC) method with fluorescence detection. Structural characterization of the metabolites was performed with HPLC and mass spectrometric detection. In our experiment extensive metabolism of CGP 41 251 was found. The presence of five hydroxylated metabolites of CGP 41 251 (I) was confirmed and two metabolites were structurally elucidated as CGP 50 750 (III) and CGP 52 421 (V). Maximal concentrations of 73 ng/ml, 1.9 ng/ml and 126 ng/ml for CGP 41 251 (I), III and V were found, respectively. The mass spectra of the other three metabolites indicate that these are oxidized nitrogens or hydroxylated compounds. As yet, the oxidation or hydroxylation sites have not been established. This study has revealed new information about CGP 41 251 pharmacokinetics and metabolism. Target levels between 10-100 ng/ml may be important to achieve in further clinical trials with CGP 41 251 as MDR modulator.