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采用超高效液相色谱-串联质谱法测定大鼠体内邻苯二甲酸二丁酯(DBP)的药代动力学。

Pharmacokinetics of dibutyl phthalate (DBP) in the rat determined by UPLC-MS/MS.

作者信息

Chang Li-Wen, Hou Mei-Ling, Tsai Tung-Hu

机构信息

Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.

出版信息

Int J Mol Sci. 2013 Jan 4;14(1):836-49. doi: 10.3390/ijms14010836.

Abstract

Dibutyl phthalate (DBP) is commonly used to increase the flexibility of plastics in industrial products. However, several plasticizers have been illegally used as clouding agents to increase dispersion of aqueous matrix in beverages. This study thus develops a rapid and validated analytical method by ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) for the evaluation of pharmacokinetics of DBP in free moving rats. The UPLC-MS/MS system equipped with positive electrospray ionization (ESI) source in multiple reaction monitoring (MRM) mode was used to monitor m/z 279.25→148.93 transitions for DBP. The limit of quantification for DBP in rat plasma and feces was 0.05 µg/mL and 0.125 µg/g, respectively. The pharmacokinetic results demonstrate that DBP appeared to have a two-compartment model in the rats; the area under concentration versus time (AUC) was 57.8 ± 5.93 min μg/mL and the distribution and elimination half-life (t(1/2,α) and t(1/2,β)) were 5.77 ± 1.14 and 217 ± 131 min, respectively, after DBP administration (30 mg/kg, i.v.). About 0.18% of the administered dose was recovered from the feces within 48 h. The pharmacokinetic behavior demonstrated that DBP was quickly degraded within 2 h, suggesting a rapid metabolism low fecal cumulative excretion in the rat.

摘要

邻苯二甲酸二丁酯(DBP)常用于提高工业产品中塑料的柔韧性。然而,有几种增塑剂被非法用作混浊剂,以增加饮料中水相基质的分散性。因此,本研究开发了一种快速且经过验证的超高效液相色谱串联质谱法(UPLC-MS/MS)分析方法,用于评估自由活动大鼠体内DBP的药代动力学。配备正电喷雾电离(ESI)源并采用多反应监测(MRM)模式的UPLC-MS/MS系统用于监测DBP的m/z 279.25→148.93跃迁。大鼠血浆和粪便中DBP的定量限分别为0.05μg/mL和0.125μg/g。药代动力学结果表明,DBP在大鼠体内似乎呈现二室模型;静脉注射(30mg/kg)DBP后,浓度-时间曲线下面积(AUC)为57.8±5.93min·μg/mL,分布半衰期和消除半衰期(t(1/2,α)和t(1/2,β))分别为5.77±1.14和217±131min。给药剂量的约0.18%在48小时内从粪便中回收。药代动力学行为表明,DBP在2小时内迅速降解,提示大鼠体内代谢迅速且粪便累积排泄量低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75aa/3565294/bcc361a3f3be/ijms-14-00836f1.jpg

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