METABOLIC STUDIES OF 2-AMINO-I,8-NAPHTHYRIDINE-3-CARBOXAMIDE
Date
1974
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ORCID
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Masters
Abstract
2-Amino-1,8-naphthyridine-3-carboxamide hydrochloride monohydrate has been shown by Hawes et all and Trethewey et al 2 to be a compound with potent diuretic and natriuretic properties without potassium loss. As the biotransformation of a compound may account for its activity, toxicity and duration of action, such a study was undertaken in the present investigation.
In this work the naphthyridine salt was administered to rats by the intraperitoneal route. The excreta of the treated rats were collected. The unchanged compound and its potential metabolites were extracted from the excreta using chloroform/isopropanol (4:1), with efficient (92%) recovery of the unchanged naphthyridine from the basified (pH 10) urine. It appeared that some glucuronides could be extracted using the present techniques. Thin layer chro-matography was used initially to for possible metabolites. Trace metabolites were detected in the screen the urine extracts quantities of possible urine and feces of the treated rats. The possible metabolites were isolated from the thin layer adsorbent by elution with methanol, and then subjected to mass spectral analysis. Positive identification of the unchanged 2-amino-1,8-naphthyridine-3-carboxamide ex-creted in the urine was made by this method. The possible
metabolites indicated by thin layer chromatography were not present in sufficient quantities to be identified by high resolution mass spectrometry. The unchanged compound was not detected in the feces. Thin layer chromatography was further investigated for its sensitivity and rapid screen-ing ability for the possible metabolites. Detection of 2-amino-1,8-naphthyridine-3-carboxamide by fluorescence, under long wave ultraviolet light, was sensitive to four nanograms. The use of Dragendorff's reagent was found to be sensitive to 0.125 micrograms, and displayed affinity for the 1,8-naphthyridine nucleus.
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Degree
Master of Science (M.Sc.)
Department
Pharmacy