title: Pharmacokinetics of di-isononyl phthalate in freely moving rats by UPLC-MS/MS.
abstract: Di-isononyl phthalate (DINP) is a general-purpose plasticizer for polyvinyl chloride. However, this industrial chemical plasticizer used as a clouding agent has recently contaminated food and beverages that had been inspected by Taiwan Food and Drug Administration. This study develops a sensitive and specific method combining ultra-performance liquid chromatography with electrospray ionization tandem mass spectrometry (UPLC-MS/MS) to investigate the pharmacokinetics of DINP in freely moving rats. Multiple reaction monitoring (MRM) was used to monitor the transition of the protonated molecule m/z of 419 [M+H](+) to the product ion 149 for DINP. The analyte was analyzed by UPLC-MS/MS with C18 column (100×2.1mm, 1.7 μm) which was equilibrated and eluted with an isocratic mixture of acetonitrile-ammonium acetate water solution (90:10, v/v) at a flow rate of 0.3 mL/min. Linear calibration curves were obtained for DINP concentration ranges of 0.05-2.5 μg/mL in plasma and feces. The feces were homogenized mechanically using 50% acetonitrile as the medium. The pharmacokinetic curve demonstrates that the disposition of DINP in rat plasma was fitted well by the two-compartment model after DINP administration (10 mg/kg, i.v.). The elimination half-life of DINP was 364±146 min and 150±58 min for intravenous (10 mg/kg) and oral (100 mg/kg) administration, respectively. The pharmacokinetic data indicate that the oral bioavailability of DINP in freely moving rats was about 1.19%. The total DINP excretion up to 48 h was 13.64±3.99% in feces.
authors.affiliation: Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Hou
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Chang
authors.forename: Chang-Jung
authors.initials: CJ
authors.lastname: Chiang
authors.forename: Yang-Hwei
authors.initials: YH
authors.lastname: Tsuang
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Tung-Hu
authors.initials: TH
authors.lastname: Tsai
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002853:Chromatography, Liquid / Q000379:methods; D005243:Feces / Q000737:chemistry; D008297:Male; D008954:Models, Biological; D010795:Phthalic Acids / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D010968:Plasticizers / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
chemical_list: D010795:Phthalic Acids; D010968:Plasticizers; C471688:diisooctyl phthalate