Metabolism and pharmacokinetics of [14C]-deoxyfructosylserotonin creatinine sulfate administered orally and intravenously to rats and mice.

Deoxyfructosylserotonin (DFS) has been shown in in vitro tests to inhibit L-DOPA-oxidase and also to suppress the multiplication of Mycobacterium leprae. The possible therapeutic use of DFS makes necessary the study of its metabolic fate in animal models. Labelled [14C]-DFS was synthesized by condensation of serotonin and [14C]-glucose and administered per os or intravenously to rats and mice. After oral administration, some of the radioactivity transited through the intestinal tract to be excreted in feces (20-60% of the dose) and some was destroyed in the pH conditions of the intestine and further metabolized by the flora, producing 14CO2 in the expired air (10-40% of the dose). Radioactivity excreted in the urine amounted to 8-15% after 24 h. After intravenous administration, 60-90% of the dose had already been excreted in the urine after 8 h. Feces and CO2 accounted for 5-10% each. In the urine, for both routes of administration, beside DFS, half of the radioactivity corresponded to the glucuronide conjugate, while in the feces all the radioactivity found was unchanged DFS. Whole animal body autoradiography showed the presence of radioactivity in all the organs (1-2% of the dose) mainly resulting from the incorporation of labelled carbon from glucose and CO2. These results, obtained in healthy rats, demonstrate poor intestinal absorption of DFS (10% of the dose) and when it is absorbed, rapid urinary excretion. For its possible therapeutic use as an anti-leprosy drug in humans, derivatives with higher bioavailability must be attained.

Mass spectrometric analysis of N-carboxymethylamino acids as periodate oxidation derivatives of Amadori compounds application to glycosylated haemoglobin.

Periodate oxidation of free and protein-bound Amadori compounds formed by the condensation of reducing sugars with primary amino groups generates, on acid hydrolysis, N-carboxymethyl derivatives of amino acids. The analysis of these modified amino acids may be used to estimate both the extent and the site of protein glycosylation. The present study describes the use of gas chromatography-mass spectrometry (GC/MS) and gas chromatographytandem mass spectrometry (GC/MS/MS) for the identification of the various N-carboxymethylamino acids. Application of this approach to the quantitation of N-carboxymethylvaline and N (ε) -carboxymethyllysine resulting from the oxidation of glycosylated haemoglobin is presented.

Improved high-performance liquid chromatographic analysis of some carboxylic acids in food and beverages as their p-nitrobenzyl esters.

An improved, straightforward and accurate method for the derivatization and quantitative high-performance liquid chromatographic analysis of carboxylic acids in food and beverages is presented. Thirty-two p-nitrobenzyl esters were prepared in high yields by direct reaction of the free acid with O-(4-nitrobenzyl)-N,N'-diisopropylisourea in dioxane-water (9:1). Benzylmalonic acid was used as a new internal standard. Excess of reagent was removed on a strong cation-exchange resin. The advantage of this original and very convenient procedure over the usual clean-up step involving filtration through a disposable silica cartridge is discussed. The p-nitrobenzyl ester derivatives were readily separated using a single linear gradient of solvent (acetonitrile in water). With a high-performance liquid chromatography column of conventional size (20-25 cm X 4.6 mm I.D.), the analysis lasted for less than 20 min. This analysis time was even shorter (less than 12 min) when using modern small-bore (100 X 2.1 mm I.D.) columns. Applications of the method to the analysis of the main carboxylic acids in coffee, wine and fruit juices are presented.