Pharmacokinetics of di-isononyl phthalate in freely moving rats by UPLC–MS/MS

• Published in: International journal of pharmaceutics Vol. 450; no. 1-2; pp. 36 - 43
• Main Authors: Hou, Mei-Ling, Chang, Li-Wen, Chiang, Chang-Jung, Tsuang, Yang-Hwei, Lin, Chi-Hung, Tsai, Tung-Hu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 25.06.2013
• Subjects: Administration, Intravenous; Administration, Oral; Animals; Biological Availability; Chromatography, Liquid - methods; Di-isononyl phthalate; Feces - chemistry; Food addition; Male; Models, Biological; Pharmacokinetics; Phthalic Acids - blood; Phthalic Acids - pharmacokinetics; Phthalic Acids - urine; Plasticizer; Plasticizers - pharmacokinetics; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Tandem mass spectrometry; Di-isononyl phthalate; Plasticizer; Food addition; Pharmacokinetics
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2013.04.033

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, 1.7μm) which was equilibrated and eluted with an isocratic mixture of acetonitrile–ammonium acetate water solution (90:10, v/v) at a flow rate of 0.3mL/min. Linear calibration curves were obtained for DINP concentration ranges of 0.05–2.5μg/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 (10mg/kg, i.v.). The elimination half-life of DINP was 364±146min and 150±58min for intravenous (10mg/kg) and oral (100mg/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 48h was 13.64±3.99% in feces.