Biomedical subjects

J F Stobaugh

Publications and source records attributed to J F Stobaugh.

41 records · Page 3Linked to original sources

PubMed1983

Factors affecting the stability of fluorescent isoindoles derived from reaction of o-phthalaldehyde and hydroxyalkylthiols with primary amines.

The stability of a series of fluorescent isoindole derivatives formed in situ under analytical conditions following the reaction of o-phthalaldehyde (OPA) and 2-mercaptoethanol (2-ME) with a series of primary amines are reported. Increasing the bulk and degree of substitution at C-10 of the resulting isoindole resulted in substantial increases in product stability. The effects of excess OPA and 2-ME on isoindole stability were examined and OPA was observed to catalyze isoindole degradation while 2-ME had no effect. Previously proposed degradation mechanisms were reexamined in light of the present data and an alternate degradation pathway is proposed. 3-Mercapto-1-propanol (3-MP) was found to be a superior thiol for use in the fluorogenic OPA reaction. The OPA/3-MP reagent combination was utilized to derive several amino acids and offered detection limits (S/N = 2) of less than 200 fmol.

Aldehydes↗

PubMed1982

Synthesis and biological evaluation of gem-dichlorocyclopropyl and cyclopropyl analogs of stilbene congeners as potential antiestrogens.

A series of gem-cichlorocyclopropyl and cyclopropyl analogs of stilbene congeners was synthesized and examined for estrogenic and antiestrogenic activity using the uterotropic assay in the immature mouse. The relative receptor affinity in vitro was determined by measuring [3H]estradiol displacement from the rat uterine cytosol receptor. The 11 test compounds synthesized in this study did not produce estrogenic or antiestrogenic activity at the dosage levels used (1-25 micrograms), but did produce a significant displacement of [3H]estradiol in the rat uterine receptor binding assay with analog XVIII possessing the greatest binding affinity and compound XI the lowest affinity. Structure-affinity relationships of this series were established from the receptor binding assay and comparisons between these analogs and a previously reported series are summarized.

Animals↗

PubMedDate not supplied

Chiral separations of enantiomeric pharmaceuticals by capillary electrophoresis using sulphobutyl ether beta-cyclodextrin as isomer selector.

Capillary electrophoresis has developed into an extremely useful technique for the separation of optical isomers. High efficiencies and the availability of many types of isomer selectors allowing rapid and inexpensive methods development make capillary electrophoresis (CE) an attractive alternative to gas chromatography (GC) and high-pressure liquid chromatography (HPLC) for the determination of chiral purity. In this research the separation of the enantiomers of some chiral pharmaceuticals was investigated using anionic sulphobutyl ether-beta-cyclodextrins as isomer selectors. These chiral selectors have a large countercurrent mobility, making them inherently advantageous as selectors as compared to neutral cyclodextrins. The effects of pH, buffer composition and selector concentration on the chiral separation of these compounds was investigated. All of the compounds studied were successfully resolved by the sulphobutyl ether beta-cyclodextrins (SBE-beta-CDs) typically with run times of less than 20 min using low concentrations of the SBE selector (1-5 mM).

Atenolol↗

PubMedDate not supplied

Rapid optimization of the post-column fluorogenic ninhydrin reaction for the HPLC-based determination of bradykinin and related fragments.

A flow injection analysis scheme is demonstrated for the rapid optimization of reagent concentrations, flow rates, delay time and temperature using the guanidino moiety specific fluorogenic ninhydrin reaction. Using the amino acid arginine, non-arginine containing peptides, and the arginine-containing peptides, bradykinin and related fragments, specificity is demonstrated. These results serve to extend previous descriptions of the post-column reaction by offering a time efficient approach for the optimization of newly assembled post-column reactors using this chemistry. The reactor is subsequently added to a gradient elution HPLC system with the separation of bradykinin and bradykinin fragments demonstrated. Detection sensitivity in the high femtomole-low picomole mass range was achieved for these substances.

Bradykinin↗

PubMedDate not supplied

Reversed-phase liquid chromatography of the opioid peptides. 3. Development of a microanalytical system for opioid peptides involving microbore liquid chromatography, post-column derivatization and laser-induced fluorescence detection.

A microanalytical system has been developed for the determination of peptides in small samples. Naphthalene-2,3-dicarboxaldehyde-beta-mercaptoethanol (NDA-BME) was used as the labelling reagent system as an alternative to NDA-cyanide (NDA-CN) because of the faster labelling when CN was replaced by a thiol. The fluorescence characteristics of the NDA-thiol adducts, N-substituted 1-alkylthiobenz[f]isoindoles (TBIs), were found to be different from the previously described cyanobenz[f]isoindole (CBIs) adducts formed by the reaction of primary amines with NDA-CN. The excitation maximum of the TBI adducts was at 460 nm, which was closer to the 457.9 nm argon-ion laser line, than the 440-nm maximum of the CBI adduct. The limit of detection for leucine enkephalin was 36 fmol (S/N = 3) and linearity was proven for greater than 2 orders of magnitude, from 45 fmol to 9 pmol for an injection volume of 60 nl. The detectability was limited by the high background noise produced by the post-column derivatization system. The utility of the system was demonstrated for the analysis of methionine enkephalin and its potential oxidation products, using leucine enkephalin as a suitable internal standard.

Chromatography, Liquid↗