betadex and propionic-acid

The enantio-separations of eight 2-arylpropionic acid nonsteroidal anti-inflammatory drugs (2-APA NSAIDs) were established using reversed-phase high-performance liquid chromatography with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as chiral mobile phase additive for studying the stereoselective skin permeation of suprofen, ketoprofen, naproxen, indoprofen, fenoprofen, furbiprofen, ibuprofen and carprofen. The effects of the mobile phase composition, concentration of HP-beta-CD and column temperature on retention and enantioselective separation were investigated. With 2-APA NSAIDs as acidic analytes, the retention times and resolutions of the enantiomers were strongly related to the pH of the mobile phase. In addition, both the concentration of HP-beta-CD and temperature had a great effect on retention time, but only a slight or almost no effect on resolutions of the analytes. Enantioseparations were achieved on a Shimpack CLC-ODS (150 x 4.6 mm i.d., 5 microm) column. The mobile phase was a mixture of methanol and phosphate buffer (pH 4.0-5.5, 20 mM) containing 25 mM HP-beta-CD. This method was flexible, simple and economically advantageous over the use of chiral stationary phase, and was successfully applied to the enantioselective determination of the racemic 2-APA NSAIDs in an enantioselective skin permeation study.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Chromatography, High Pressure Liquid; Propionates; Stereoisomerism

The aim of this study was to evaluate the influence of dietary propionic acid and bile acid excretion on the hypocholesterolemic effect of fibers. For this purpose, rats were adapted to a diet containing 10 g inulin, 10 g beta-cyclodextrin, or 2.5 g calcium propionate per 100 g diet. Both the inulin and beta-cyclodextrin diets elicited high propionic acid fermentations in the cecum (approximately 45% of total short-chain fatty acids) with relatively low molar proportions of acetic and butyric acids. In rats fed the three experimental diets, 5-7 mumol/min of propionic acid was absorbed in the portal vein, and propionic acid was entirely metabolized by the liver. Plasma cholesterol was more effectively depressed by the beta-cyclodextrin diet than by the inulin diet; the propionic acid-supplemented diet was ineffective in this respect. The inulin diet slightly increased fecal bile acid excretion, compared with the control diet, whereas beta-cyclodextrin markedly enhanced (1.8-fold) bile acid excretion. Microsomal hydroxymethylglutaryl-CoA (HMG-CoA) reductase activity was slightly depressed in rats fed the propionic acid-supplemented diet, whereas it was enhanced by the beta-cyclodextrin diet in parallel to the activity of cholesterol 7 alpha-hydroxylase. The present data suggest that absorption and further hepatic metabolism of large amounts of propionic acid are not sufficient to counteract the induction of HMG-CoA reductase resulting from bile acid fecal losses. The rise of these losses plays a major role in the hypocholesterolemic effect of beta-cyclodextrin.

Topics: Absorption; Animals; beta-Cyclodextrins; Bile Acids and Salts; Cecum; Cholesterol; Cyclodextrins; Diet; Dietary Fiber; Feces; Fermentation; Hydroxymethylglutaryl CoA Reductases; Inulin; Liver; Male; Oligosaccharides; Propionates; Rats; Rats, Wistar