Search PubMed⌕ Search

Biomedical subjects

C Aubert

Publications and source records attributed to C Aubert.

At least 109 records · Page 6Linked to original sources
PubMed1982

Quantitative analysis of 5-fluorouracil and 5,6-dihydrofluorouracil in plasma by gas chromatography mass spectrometry.

5-Fluorouracil and 5,6-dihydro-5-fluorouracil were analysed in the plasma of patients by combined gas chromatography mass spectrometry. 5-Bromouracil was the internal standard. After extraction from plasma with an isopropanol-diethyl ether mixture (20/80) the components were pentylated and the derivatives produced extracted into diethyl ether. Electron impact mass spectrometry was used for the simultaneous quantitative determinations of 5-fluorouracil and 5,6-dihydro-5-fluorouracil (detection limit 10 ng ml-1 5-fluorouracil, 80 ng ml-1 5,6-dihydro-5-fluorouracil). Chemical ionization was utilized to measure 5,6-dihydro-5-fluorouracil concentrations less than 80 ng ml-1 (sensitivity 10 ng ml-1). The biological applicability of these two techniques was demonstrated by analysing plasma samples from patients after administration of 5-fluorouracil or 5'-deoxyfluorouridine by intravenous injections and infusions.

Chromatography, High Pressure Liquid↗
PubMed1982

Highly specific and sensitive method for the determination of flunitrazepam in plasma by electron capture gas-liquid chromatography.

A sensitive and highly specific electron capture gas-liquid chromatographic method was developed for the determination of flunitrazepam in human plasma. The method involves selective extraction of the drug into hexane from plasma at pH 9 followed by back-extraction into 2 N sulfuric acid for clean-up procedure, and re-extraction by 20% toluene-hexane at pH 2. The sensitivity limit of the method is 0.5 ng/ml of plasma. Its specificity was tested for about 45 drugs frequently administered as co-medication in hospitalized patients, including other benzodiazepines. The method proves very suitable for investigating the clinical pharmacokinetics of flunitrazepam as well as for monitoring therapeutic plasma levels and in forensic situations following over-dosage, and was successfully applied within a clinical pharmacokinetic study in an intensive care unit.

Anti-Anxiety Agents↗
PubMed1982

Simultaneous plasma levels determination of mexiletine and one of its metabolites by electron capture gas-liquid chromatography.

A sensitive and specific electron capture gas-liquid chromatographic method is developed for the determination in human plasma both of mexiletine and of one of its hydroxymethyl metabolites appearing progressively during the kinetics and the presence of which is characterized by mass spectrometry. This method involves the use of two internal standards and the extraction of the drug and of its metabolite from alkaline plasma with diethyl ether followed by back extraction into sulfuric acid (0.2 N) for clean-up procedure and re-extraction by diethyl ether. The limits of detection of the heptafluorobutyryl derivatives of mexiletine and of its metabolite are 20 and 7 ng/ml of plasma, respectively. The preliminary results of the pharmacokinetic study performed in a cardiological unit after single oral administration and during long-term oral maintenance therapy are described in this paper. The method makes it possible to get a better knowledge of the kinetic behaviour of mexiletine and of its metabolite and contributes to the understanding of the origins of the variable pharmacokinetics of mexiletine in patients.

Arrhythmias, Cardiac↗
PubMed1981

Comparative determinations of 5-fluorouracil in plasma using GC/MS and HPLC.

Gas chromatography-mass spectrometry (GC/MS) and high performance liquid chromatography (HPLC) procedures have developed to determine 5-fluorouracil (5-FU) in human plasmas. Internal standard in both systems was 5-bromouracil (5-BrU). The HPLC assay used an extracted plasma with an ether-isopropanol mixture (75-25): the analyses were performed on a mu Porasil column (10 micrometer) with hexane-ethanol (75-25) as elution solvent (detection limit 50 ng/ml). For GC/MS, after precipitation of proteins, the plasma was purified through a microcolumn packed with AG1 X 4 resin, and then the components were methylated. Electron impact (EI) and selective ion monitoring (SIM) mode was retained for GC/MS quantitative studies (detection limit 5 ng/ml). Moreover, the authors compared these two techniques by measurements on plasma samples obtained from patients after rapid i.v. injections, infusions and p.o. administration.

Administration, Oral↗
PubMed1981

Advantages and limitations of pharmacokinetic studies in the rationalization of anticancer therapy: methotrexate and 5-FU.

The use of pharmacokinetic studies for individual dose regimen adjustments in anticancer therapy is considered. The example of methotrexate in the treatment of head and neck tumors demonstrates the validity of this approach. Moreover, the importance of biotransformations of this antimetabolite is confirmed using a high pressure liquid chromatography assay. The example of 5-FU outlines the analytical and mathematical difficulties rendering this approach unlikely for routine use. Some preliminary relations between pharmacokinetic parameters (plasma clearance) and clinical response are presented. The determination of the main plasma metabolic 5-6 dihydro 5-FU by GC/MS and its possible role in the nonlinear pharmacokinetics of the drug in therapeutic failure are discussed.

Drug Administration Schedule↗
PubMed1980

Melanogenesis in cultured human neuroblastomas.

The catecholic amino acids, dopa and 5-S-cysteinyldopa, and the dopamine metabolite, homovanillic acid, were determined in 8 neuroblastomas. 5-S-Cysteinyldopa and/or dopa were detected in all cases and homovanillic acid was present in 5. Dopa was also found in two tumours in which no definite histological diagnosis could be made. Neuroblastoma cells were cultured from 7 patients. The ageing of human sympathoblasts in culture was accompanied by modifications in the ability to synthetize dopa, which is a precursor of catecholamines as well as of melanins, and the metabolite homovanillic acid. An increase in the levels of 5-S-cysteinyldopa, a metabolite of the melanocytes, has been observed. Concurrent modifications of ultrastructural morphology with the disappearance of granular vesicles and appearance of melanosomes were noticed. This modulation of the original phenotypic expression commonly resulted in cell death, but in one case of metastatic adenopathy of a neuroblastoma we have been able to establish a permanent pigmented cell line.

Animals↗
PubMed1980

Tumorigenicity of human malignant melanocytes in nude mice in relation to their differentiation in vitro.

Of 16 cell lines derived from 12 human melanomas obtained from 11 patients, all were established as permanent cell lines: 7 from primary tumors and 9 from metastatic tumors. Study of the early subcultures and established cell lines showed that melanocytes passed through a phase of dedifferentiation during which they took on a fibroblast-like appearance and were hypodiploid and nontumorigenic in nude (thymus-deficient) mice. Phenotypic modulation in vitro was shown to be dependent on the culture medium. The lines varied considerably in karyologic and phenotypic expression (as assessed by morphologic appearance and 5-S-cysteinyldopa production). Fibroblast-like, epithelioid, nonpigmented, achromic, and pigmented cells were obtained from the same tumor. Heterotransplantation into nude mice revealed wide variations in tumorigenicity: The latency of the tumors, their size, and infrequent metastases bore no relationship to the phenotypic modulation of the melanocytes as expressed in vitro. Melanogenesis is therefore not related to malignancy; they are two independent characteristics.

Animals↗