PubMed Health⌕ Search

Biomedical subjects

M G Vargas

Publications and source records attributed to M G Vargas.

9 recordsLinked to original sources
PubMed2000

Fast development of separation methods for the chiral analysis of amino acid derivatives using capillary electrophoresis and experimental designs.

The use of experimental design in method development was studied for the chiral separation of several amino acid derivatives with capillary electrophoresis. The aim of this study was to define rapidly experimental conditions under which the enantiomers can be sufficiently separated for quantification and to derive a methodology for the separation of new compounds. Three modified cyclodextrins (CDs) were used as chiral selectors: hydroxypropyl-beta-cyclodextrin, carboxymethyl-beta-CD and sulfobutylether-beta-CD. The following factors were examined: the type of cyclodextrin, the CD concentration, the pH and the % of organic modifier (methanol) of the electrolyte. Two types of fractional factorial design were used depending on the type of analyte and on the number of factors selected: a 3(4-2) fractional factorial design (4 factors studied at 3 different levels) and a 2(3-1) fractional factorial design (3 factors at 2 different levels). From the 14 compounds investigated, 12 could be separated with one or another CD and not more than 9 experiments were required. No generalisation of the best analysis conditions was possible within this family of compounds. Specific analysis conditions must be defined for each analyte. Experimental designs have shown to be very useful to determine rapidly conditions under which each enantiomer can be separated with an acceptable resolution.

Amino Acids↗
PubMed1999

Rapid development of the enantiomeric separation of beta-blockers by capillary electrophoresis using an experimental design approach.

A rapid method for determining the separation conditions for chiral resolution of eleven beta-blocking drug substances by capillary electrophoresis is described, using an experimental design approach. An acidic phosphate-triethanolamine buffer and an uncoated fused-silica capillary were used for all experiments. Several modified cyclodextrins were applied as chiral selectors: sulfobutyl ether beta-cyclodextrin (SBE-beta CD), dimethyl beta-cyclodextrin (DM-beta CD), carboxymethyl beta-cyclodextrin (CM-beta CD), and hydroxypropyl beta-cyclodextrin (HP-beta CD). Two different fractional factorial experimental designs were applied: (1) a design examining four factors at three levels (3(4-2)) and (2) one examining three factors at two levels (2(3-1)). The factors studied were: type of cyclodextrin, cyclodextrin concentration, pH of the background electrolyte and percentage of organic modifier. Enough resolution for the separation of the enantiomers and even for their quantification was reached. The same scheme is proposed when a fast chiral separation method needs to be developed for other drug families.

Adrenergic beta-Antagonists↗
PubMed1998

Capillary zone electrophoretic determination of some drugs against Alzheimer's disease.

A new capillary zone electrophoresis (CZE) method for the determination of tacrine (THA), 7-methoxytacrine (7-MTHA) and their basic metabolites (THAm, 7-MTHAm) in pharmaceutical and biological samples (urine and serum) was developed. Separation of all compounds by CZE was carried out using a 46.6 cm untreated fused-silica capillary applying 20 kV separation voltage using 50 mM phosphate buffer of pH 2.8 for THA and THAm and of pH 7.8 for 7-MTHA and 7-MTHAm as background electrolyte (BGE). Detection was carried out at 240 nm (THA and THAm) and 248 nm (7-MTHA and 7-MTHAm). THA and THAm were separated in less than 4 min while 7-MTHA and 7-MTHAm were separated in less than 7 min. The detection limits (SIN = 3) obtained were 3 ppb for THA and 4 ppb for 7-MTHA in aqueous solutions; 50 ppb for THA and 47 ppb for 7-MTHA for the determination in urine (diluted 1:10); 52 ppb for THA and 56 ppb for 7-MTHA, in deproteinized serum samples. The methods are suitable for therapeutic drug monitoring of the drugs.

Alzheimer Disease↗
PubMed1996

Alterations of cAMP response element-binding activity in the aged rat brain in response to administration of rolipram, a cAMP-specific phosphodiesterase inhibitor.

Transcription factor, cAMP response element-binding protein (CREB), which is phosphorylated by cAMP-dependent kinase via an increase in cAMP, and regulates gene transcription by binding to the cAMP response element (CRE) on target genes. We examined age-dependent alterations in the DNA-binding activity of CREB in rat brain regions, and the effects of rolipram, a cAMP-specific phosphodiesterase (PDE) inhibitor on the CRE-binding activity by electrophoretic mobility-shift assay (EMSA). A marked age-dependent decrease in the CRE-binding activity was shown in all brain regions examined, especially in the basal forebrain, the striatum and the hippocampus. Furthermore, CRE-binding activities in the basal forebrain of both young-adult and aged rats significantly increased 2 h after rolipram administration (1 mg/kg, i.p.), and the rolipram treatment recovered the decreased CRE-binding activity in the aged rats. The saturation experiment in EMSA also revealed that rolipram reversed the decrease in the maximum CRE-bindings in the basal forebrain with aging. Since the 5' upstream region of the rat choline acetyltransferase (ChAT) gene contains CRE, and ChAT-positive neurons in the basal forebrain project to the frontal cortex and the hippocampus, rolipram may exert its previously reported ameliorating effect on the age-related reductions of ChAT activities in the frontal cortex and the hippocampus by phosphorylating CREB in the basal forebrain with activation of cAMP-dependent protein kinase via inhibition of PDE.

Afferent Pathways↗
PubMed1976

Evaluation of enzyme-multiplied immunoassay technique (EMIT) for determination of serum digoxin.

Sixty-seven digoxin-containing sera were analyzed by both radioimmunoassay and EMIT. After some important modifications of the EMIT method, agreement between the two methods was very good. Reproducibility of the EMIT assay was excellent; daily variations in values found for control sera were quite small, and recovery of added digoxin was good. Slight hemolysis hadnegligible effects, but highly hemolyzed specimens gave low recoveries of digoxin.

Digoxin↗