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

(1)A建立了高效液相色谱-荧光检测法测定减肥药芬氟拉明及其代谢物去甲芬氟拉明和苯乙哌啶的含量。这些化合物的检测下限为23 fmol/20 μ l进样，信噪比为3。与单剂量Phen相比，与Fen联合给药时，脑中Phen的AUC增加了3.4倍。血药浓度AUC增加2.2 ~ 2.6倍。另一方面，芬浓度不受共同管理的Phen。(2)An建立了高效液相色谱-荧光法测定减肥药马吲哚及其代谢产物2-（2-氨乙基）-3-（对氯苯基）-3-羟基苯甲脒的含量，并应用于小鼠脑组织和血浆中马吲哚及其代谢产物的分析。在此基础上建立了一种高灵敏度测定大鼠毛发中芬氟醚和诺氟醚的方法，并成功地应用于大鼠服用N-亚硝基芬氟胺后毛发中芬氟醚和诺氟醚的分析。（3）对健康食品中摄入N-Fen的肝病患者的头发样本进行分析。测定的所有样品均含有芬和诺氟沙星。通过对头发样本的分段分析，阐明了患者的长期摄入。（4）苯丙醇胺是一种治疗肥胖和鼻粘膜炎的药物，已被证实可引起脑出血的副作用。因此，它被禁止用作药物。本研究建立了一种高灵敏度的测定方法，以阐明其不良反应的发生机制。PPA的药代动力学参数受到咖啡因和氯苯那敏联合给药的影响;观察到咖啡因和氯苯那敏的脑AUC分别增加1.6倍和1.5倍。与PPA单剂量相比，bdh化合物的联合给药使AUC增加1.9倍。另一方面，对于血液，

(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