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Biomedical subjects

C F Gelijkens

Publications and source records attributed to C F Gelijkens.

10 recordsLinked to original sources
PubMed1985

The use and limitations of deuterated lorcainide in metabolism and pharmacokinetic studies.

Lorcainide, a new antiarrhythmic agent currently undergoing clinical trial, has been pentadeuterated and the usefulness of this labelled compound in pharmacokinetic and metabolism studies has been investigated in dogs. Specific analytical methods based on capillary gas chromatography/mass spectrometry (GC/MS) were developed for quantitative and qualitative analysis of plasma and urine samples. Following oral administration of an equimolar mixture of 5 : 5 mg of (2H0/2H5)lorcainide, eight major metabolites were rapidly identified in urine by the ion cluster technique. Quantitative analysis of (2H0/2H5)lorcainide in plasma and urine indicated an enhanced systematic availability of the deuterated compound, probably due to a secondary isotope effect. According to these findings in the dog, the use of deuterated lorcainide in human bioavailability and metabolism studies is probably of limited value.

Animals↗
PubMed1980

Reverse-phase liquid chromatography of 5-fluorouracil nucleosides and nucleotides in the presence of quaternary ammonium ions.

Reversed-phase liquid chromatography is used for the separation of 5-fluorouracil, its deoxyribo- and ribonucleosides and nucleotides. The bases and nucleosides are easily separated from their naturally occurring analogues on an octadecyl silica column eluted with 2.10(-2) M KH2PO4 (pH 5.0) containing 5% (v/v) of methanol. This system can be applied to the measurement of 5-fluoro-2'-deoxyuridine serum levels down to 0.1 microgram/ml. Addition of small amounts (10(-3) M) of tetrabutylammonium phosphate to the eluent results in a large retention increase for the nucleotides, while the capacity ratios of the bases and nucleosides remain unchanged. The influence of the tetrabutylammonium phosphate and ammonium phosphate concentrations and pH of the eluent on the various k' values was investigated. Evidence is presented indicating that the quaternary ammonium compound is adsorbed onto the octadecyl silica surface: nucleotides are probably retained as adsorbed tetrabutylammonium ion-pairs.

Chromatography, Liquid↗
PubMed1980

Measurement of 5-fluoro-2'-deoxyuridine serum levels by gas chromatography chemical ionization mass spectrometry.

Serum levels of 5-fluoro-2'-deoxyuridine in cancer treated patients were measured by gas chromatography mass spectrometry under chemical ionization conditions; 1-(2-deoxy-beta-D-lyxofuranosyl)-5-fluorouracil (3'-epi-5-fluoro-2'-deoxyuridine) was used as an internal standard. The drug and internal standard were quantitatively isolated from the serum sample by a mini-column anion exchange method and the extract permethylated using potassium-tert-butoxide in dimethylsulphoxide and methyl iodide. The derivatized nucleosides were then re-extracted from the reaction mixture and analysed on a glass capillary column coated with Superox-4. The column was coupled directly to the chemical ionization source of the mass spectrometer; NH3 was used as the reagent gas. The gas chromatographic effluent was monitored at m/z 289, the [MH]+ ion of the N,O-permethyl derivatives of 5-fluoro-2'-deoxyuridine and the internal standard. Recovery of 5-fluoro-2'-deoxyuridine from serum in the 0-1 microgram ml-1 concentration range averaged 93 +/- 2% (SD); a linear detector response was observed up to 50 ng 5-fluoro-2'-deoxyuridine ml-1. At the 10 ng ml-1 level, a within-run assay precision of 10% (CV) (n = 5) was found, while a detection limit of about 1 ng 5-fluoro-2'-deoxyuridine ml-1 of serum was attained. The method was applied to the measurement of disappearance curves of 5-fluoro-2'-deoxyuridine in the serum of treated patients.

Floxuridine↗
PubMed1978

Quantification of 5-fluorouridine in human urine by capillary gas-liquid chromatography with a nitrogen-selective detector.

A method for the quantitative determination of 5-fluorouridine (I) in human urine is presented. The analysis involves the isolation of 5-fluorouridine and the internal standard, 5-chlorouridine (II), on immobilized phenylboronic acid; the extract is further purified by mini-column anion exchange chromatography. The resulting methanolic eluate is evaporated to dryness, the residue is dissolved in dimethyl sulfoxide and permethylated using potassium-t-butoxide and methyl iodide. The permethyl derivatives of the nucleosides are reextracted from the reaction mixture and analyzed by GLC on a glass capillary column coupled to a nitrogen-selective detector. Analytical recovery of 5-fluorouridine added to human urine in the 0--1 microgram/ml concentration range was 68 +/- 6% and a linear detector response was obtained up to 1 microgram/ml. The detection limit was found to be 10 ng/ml, using a 1-ml urine sample.

Chromatography, Gas↗
PubMed1978

GLC determination of floxuridine in plasma using a thermionic nitrogen detector.

A specific GLC method was developed for the determination of floxuridine in plasma using the thermionic nitrogen detector. The method involves the isolation of the compound and internal standard from plasma on a strong anion-exchange column at pH 10, followed by elution with 0.3 M acetic acid in methanol. The eluate is evaporated to dryness, and the residue is dissolved in dimethyl sulfoxide and permethylated with potassium tert-butoxide and methyl iodide. The permethylated compounds are reextracted from the reaction mixture with cyclohexane-methylene dichloride (9:1). The organic solution is evaporated to dryness, the residue is dissolved in ethyl acetate, and an aliquot is analyzed by GLC on a 3% OV-17 column. The extraction recovery from spiked plasma was 93.2 +/- 2.1% (SD), whereas linearity for the overall procedure was in the 0-1-microgram/ml range. The detection limit of the thermionic nitrogen detector was 50 ng/ml. The within-run and within days precision (CV) were 4.0 and 6.2%, respectively, at 300 ng/ml.

Chromatography, Gas↗
PubMedDate not supplied

Identification and quantitation of 5-fluorouridine in rat urine after administration of 5-fluorouracil or 5-fluoro-2'-deoxyuridine.

The ribonucleoside 5-fluorouridine was identified in 24-hr urine samples from rats after ip administration of 5-fluorouracil (200 mg/kg) or 5-fluoro-2'-deoxyuridine (380 mg/kg) by means of thin-layer chromatography, high-pressure liquid chromatography, capillary gas-liquid chromatography and gas-liquid chromatography-mass spectrometry techniques, and by comparison with the synthetic compound. By use of a specific extraction procedure, 5-fluorouridine was then quantitatively determined by capillary gas-liquid chromatography with a nitrogen-selective detector. These measurements indicate that not more than 0.2% of the administered dose was excreted as 5-fluorouridine; lower urinary metabolite levels were found after treatment with 5-fluorouracil than after 5-fluoro-2'-deoxyuridine administration. Following an ip dose of either drug, variable amounts of 2'-deoxyuridine and thymidine were detected in the urine samples.

Animals↗