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Pharmacokinetics and metabolism for the alternatives to endocrine disrupting chemicals

Pharmacokinetics and metabolism for the alternatives to endocrine disrupting chemicals
Other Titles
환경호르몬 대체물질의 체내동태 및 대사 연구
Hyeon Kim
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Nonylphenol and phthalates are well known for endocrine disrupting chemicals. These chemicals are known to have a harmful effects on ecosystems and the human body. To replace these chemicals, octyl-β-D-glucopyranoside (OG), octaethylene glycol monodecyl ether (C10E8) and acetyl triethyl citrate (ATEC) were selected as alternative materials, and their pharmacokinetic properties were characterized. For pharmacokinetic study, a bioanalytical method was developed in liquid chromatography-tandem mass spectrometric (LC-MS/MS) for three types of materials, and the stability evaluation was performed in plasma and rat and human liver microsomes. Plasma was obtained after oral and intravenous administration of the alternative materials in rats. After the concentration of the alternative materials in plasma was quantified, parmacokinetic parameters were calculated. Urine and feces were collected using metabolic cage after oral administration. Metabolic identification, profiling and pattern analysis of alternative materials also were carried out in plasma, urine and feces using LC/QTOF/MS. As a results, OG was relatively stable in biological samples but easily degraded in intestinal environment. After oral and intravenous administration in rats, OG was rapidly eliminated. Metabolites of OG were mainly produced by hydroxylation. C10E8 was stable in plasma but was easily metabolized by liver microsomes. Pharmacokinetic results of C10E8 showed that both parent compound and metabolites were easily excreted from the body. The metabolites of C10E8 were formed by hydrolysis, oxidation, and carboxylation. ATEC was very unstable in biological sample, and it was found to be easily excreted from the body. The metabolites of ATEC were mainly formed by hydrolysis. These results may be helpful for understanding the safety and toxicity of alternatives to endocrine disrupting chemicals.
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GRADUATE SCHOOL[S](대학원) > PHARMACY(약학과) > Theses (Ph.D.)
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