Determination of fluorine in organic and inorganic pharmaceutical compounds by high resolution nuclear magnetic resonance spectrometry interfaced with a computer system.
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Biomedical subjects
Publications and source records attributed to A D Bender.
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The intent of this study was to determine what influence, if any, increasing age has on the binding of drugs by plasma proteins. Plasma from healthy subjects ranging in age from 21 to 94 years was used. The binding of phenytoin (diphenylhydantoin) (acid), penicillin G potassium (benzylpenicillin potassium), and phenobarbituric acid was determined by equilibrium dialysis of 14C-labeled compounds. No differences were found in total protein concentration; however, albumin was reduced in subjects over 50 years of age. Plasma binding of each drug studied was not related to age; this finding suggests that age per se is not a factor in the binding of drugs by plasma proteins.
In the search for prostaglandin-like structures capable of exerting specific and desirable biological properties, a variety of simple heterocyclic homoprostanoidal derivatives was synthesized from readily available stearic acid derivatives. Compounds 5b and 5e were found to be more than 100 times as potent as PGE1 and PGE2 in a tracheal chain bioassay and, like 6, 9, and 12, inhibited PGE2-induced diarrhea. Derivatives 6 and 7a showed significant PG-synthetase inhibitor activity.
Reverse phase high speed liquid chromatographic methods are presented for the separation and detection of cephalosporins, penicillins, tetracyclines and other miscellaneous antibiotics. The reverse phase approach is superior to ion-exchange liquid chromatography and spectrophotometric, chemical and microbiological procedures currently in use. In addition to being simple and easy to control, the technique is rapid, convenient and precise and provides the basis for the direct analysis of pure compounds, stability samples, complex mixtures and dosage forms of all types. Preparative chromatography has been used in our laboratory for the separation and isolation of up to 500 mg of antibiotics. Using this approach, we have separated and isolated small impurities as well as pure feference compounds. The methodology reported here can be extensively applied to the separation, quantitation and isolation of both naturally occurring and synthetically produced antibiotics in a variety of media including physiological fluids.
A group of tricyclic analogs of flufenamic acid were tested for their ability to inhibit both the biosynthesis of prostaglandin and carrageenan-induced inflammation of the rat paw. All had activity greater than phenylbutazone as inhibitors of prostaglandin synthetase, with SK&F 22908 being as active as flufenamic acid. The anti-inflammatory activities of these compounds correlated only to a minor degree with the inhibition of prostaglandin biosynthesis. The data support the position that within this series of compounds inhibition of prostaglandin synthetase and non-steroidal antiinflammatory activity, as well as ulcerogenic liability, may be an expression of different mechanisms.
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