Development of analytical methods for the detarmination of obssity drugs in a small amount of biological samples

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(1)A practical HPLC method with fluorescence detection for the determination of bbesity drugs such as fenfluramine(Fen) and its metabolite norfenfluramine(Norf), and phentennine Phen) was developed. The lower detection limits of these compounds were 23 fmol per 20 μ1 injection at a signal-to-noise ratio of 3. Concentration of Phen in brain increased 3.4 times in AUC by co-administration of Fen compared to single dose of Phen. Blood concentration increased 2.2〜2.6 times in AUC. On the other hand, Fen concentration was not influenced by co-administration of Phen.(2)An HPLC-FL method for the determination of an obesity drug mazindole, and its metabolite 2-(2-amnoethyl)-3-(p-chlorophenyl)-3-hiydroxyphtalimidine was developed and applied to their analysis in mouse brain and plasma samples. Further a high sensitive method for the determination of Fen and Norf in rat hair was developed, and successfully applied to their analysis in hair after administration of N-nitrosofenfluramine(N-Fen) to rat.(3)Hair samples of patients who ingested N-Fen in healthy foods and were taken liver disease were analyzed. All the samples determined contained Fen and Norf.. By the segmental analysis of the hair sample, a long ingestion by the patients has been elucidated.(4)Phenylpropanolamine, an obesity and nasal catarrh drug, has been proved to cause side effect of cerebral hemorrhage. As a result, its use as a medicine was prohibited. In this study, to clarify the mechanism of its adverse reaction, a high sensitive determination method was developed. Rharmacokinetic parameters of PPA were fairly influenced by co-administration with caffeine and chlorfeniramine ; 1.6 times increase with caffeine and 1.5 times increase with chlorfeniramine were observed in AUC for brain. OHulministration ofbdh compounds increased 1.9 times in AUC Co-administration of both compounds increased 1.9 times in AUC compared to PPA single dose. On the other hand, no significant difference was observed for blood