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Biomedical subjects

M S Leloux

Publications and source records attributed to M S Leloux.

9 recordsLinked to original sources

Quantititative determination of glycosylated and aglycon isoprenoid cytokinins at sub-picomolar levels by microcolumn liquid chromatography combined with electrospray tandem mass spectrometry.

Microcolumn liquid chromatography (microLC) combined with electrospray tandem mass spectrometry is used for the determination of intact glycosylated cytokinins and the corresponding aglycons at picomole and sub-picomole levels in plant tissue. Routine analysis was done on C8-bonded silica using a methanol-water gradient. Data acquisition was performed by multiple reaction monitoring. Quantification was carried out by using isotopically labelled analogues and applying linear regression to the response factor versus concentration data. For routine analysis a calibration range from 0.5 to 10 pmole injected on-column was used. The limits of detection ranged from 50 to 100 fmole injected on-column. The microLC procedure was used to analyse plant tissue extracts from transgenic homozygote and hemizygote as well as wild-type Nicotiana tabacum species, and cauliflower samples. The data were compared with results obtained by conventional immunoassay and a satisfactory correlation was found. Validation data are presented.

Chromatography, Affinity↗

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 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.

Gas Chromatography-Mass Spectrometry↗

The use of electron impact and positive chemical ionization mass spectrometry in the screening of beta blockers and their metabolites in human urine.

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.

Adrenergic beta-Antagonists↗

Improved screening method for beta-blockers in urine using solid-phase extraction and capillary gas chromatography-mass spectrometry.

An improved screening method for beta-blockers in urine is proposed, involving enzymatic hydrolysis, solid-phase extraction and capillary gas chromatography-mass spectrometry. Several extraction methods for beta-blockers, such as conventional liquid-liquid and solid-phase extraction procedures, have been evaluated for at least eight beta-blockers. Additionally, the gas chromatographic properties and mass fragmentation of the trimethylsilyl-trifluoroacetyl, trifluoroacetyl and cyclic n-butylboronate derivatives of beta-blockers have been compared and evaluated with respect to their efficiency for screening urine. The resulting screening method proved to be a specific and sensitive procedure, enabling these analytes to be detected and identified up to 48 h after the administration of a dosage, usually encountered in doping cases.

Adrenergic beta-Antagonists↗

Rapid chiral separation of metoprolol in plasma--application to the pharmacokinetics/pharmacodynamics of metoprolol enantiomers in the conscious goat.

The plasma concentrations of metoprolol enantiomers have been determined by means of a direct phenyl carbamate-cellulose-based chiral high performance liquid chromatography assay using fluorimetric detection. This assay has been used to investigate the pharmacokinetics and pharmacodynamics of metoprolol enantiomers in the conscious goat. There is evidence that the pharmacokinetics of metoprolol in the goat occurs stereoselectively and that enantiomer-enantiomer pharmacokinetic interactions occur. R-Metoprolol is less effective in reducing the mean arterial blood pressure than S- and R/S-metoprolol.

Animals↗

Experimental studies on thallium toxicity in rats. II--The influence of several antidotal treatments on the tissue distribution and elimination of thallium, after subacute intoxication.

The influence of several antidotal treatments--e.g. Prussian Blue + Furosemide, Furosemide, activated Charcoal, Potassium Chloride and Potassium Iodide--on the tissue distribution and elimination of thallium after subacute intoxication is studied. From these experiments, the fate of electrolytes (Na+, K+, Cl-) may be evaluated. It was established that the efficacy of an antidotal treatment in thallium intoxication may be judged not only by the determination of its ability to interfere in the reabsorption and redistribution of thallium. Prussian Blue was the only antidotal that did not cause such a dangerous redistribution.

Animals↗