食品科学

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邻苯二甲酸二(2-乙基己基)酯在青春期小鼠体内的代谢动力学研究

张 丹,叶 逵,王家家,徐 海,宋星星,金忠秀,盛 杰,李 李,刘开永*   

  1. 安徽医科大学公共卫生学院,安徽 合肥 230601
  • 出版日期:2015-03-15 发布日期:2015-03-17

Pharmacokinetics of Di-(2-ethylhexyl)phthalate in Pubertal Mice

ZHANG Dan, YE Kui, WANG Jiajia, XU Hai, SONG Xingxing, JIN Zhongxiu, SHENG Jie, LI Li, LIU Kaiyong*   

  1. School of Public Health, Anhui Medical University, Hefei 230601, China
  • Online:2015-03-15 Published:2015-03-17

摘要:

研究邻苯二甲酸二(2-乙基己基)酯(di-(2-ethylhexyl)phthalate,DEHP)在青春期小鼠体内的代谢动力学,以300 mg/kg DEHP灌胃青春期小鼠,血清样品经固相萃取(solid phase extraction,SPE)提取和净化,气相色谱-质谱联用(gas chromatography-mass spectrometry,GC-MS)法测定不同时间点的血药质量浓度,以3p97软件拟合其动力学参数。DEHP在青春期小鼠体内的主要药物代谢动力学参数:药峰质量浓度ρmax为(0.476±0.028) μg/mL,达峰时间Tpeak为(2.539±0.424) h,药-时曲线下面积AUC(0-t)为(32.209±11.220) h•μg/mL,分布半衰期t1/2α为(1.886±0.480) h,消除半衰期t1/2β为(36.473±8.324) h。本方法简便快捷,其灵敏度和准确度均可满足青春期小鼠体内DEHP代谢动力学研究。DEHP在青春期小鼠体内药物代谢动力学过程符合一级吸收二室开放模型,其分布较快,代谢较慢。

关键词: 药物代谢动力学, 气相色谱-质谱联用, 固相萃取, 邻苯二甲酸二(2-乙基己基)酯

Abstract:

A pharmacokinetic study of di-(2-ethylhexyl)phthalate (DEHP) was carried out in pubertal mice. The serum of
pubertal mice was collected after oral administration of DEHP at a dose of 300 mg/kg, and DEHP was extracted from the
serum samples and purified by solid phase extraction (SPE). The DEHP concentrations in serum at different time points
were assayed by gas chromatography-mass spectrometry (GC-MS) and the pharmacokinetic parameters were calculated by
3p97 software. The major pharmacokinetic parameters of DEHP in pubertal mice were obtained as follows: ρmax (0.476 ±
0.028) μg/mL, Tpeak (2.539 ± 0.424) h, AUC(0-t) (32.209 ± 11.220) h·μg/mL, t1/2α (1.886 ± 0.480) h, and t1/2β (36.473 ±
8.324) h. The method presented is sensitive, accurate and fast, and can meet the requirements for the pharmacokinetic study
of DEHP in pubertal mice. The pharmacokinetics of DEHP in pubertal mice was found to be fitted to a two-compartment
open model with first order absorption and DEHP reveals the quick distribution and slow elimination.

Key words: pharmacokinetics, gas chromatography-mass spectrometry, solid-phase extraction, di-(2-ethylhexyl) phthalate (DEHP)

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