title: Determination and pharmacokinetics of di-(2-ethylhexyl) phthalate in rats by ultra performance liquid chromatography with tandem mass spectrometry.
abstract: Di-(2-ethylhexyl) phthalate (DEHP) is used to increase the ﬂexibility of plastics for industrial products. However, the illegal use of the plasticizer DEHP in food and drinks has been reported in Taiwan in 2011. In order to assess the exact extent of the absorption of DEHP via the oral route, the aim of this study is to develop a reliable and validated ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method to evaluate the oral bioavailability of DEHP in rats. The optimal chromatographic separation of DEHP and butyl benzyl phthalate (BBP; used as internal standard) were achieved on a C₁₈ column. The mobile phase was consisted of 5 mM ammonium acetate-methanol (11:89, v/v) with a flow rate of 0.25 mL/min. The monitoring ion transitions were m/z 391.4 → 149.0 for DEHP and m/z 313.3 → 149.0 for BBP. The mean matrix effects of DEHP at low, medium and high concentrations were 94.5 ± 5.7% and 100.1 ± 2.3% in plasma and feces homogenate samples, respectively. In conclusion, the validated UPLC-MS/MS method is suitable for analyzing the rat plasma sample of DEHP and the oral bioavailability of DEHP was about 7% in rats.
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St, Beitou District, Taipei 112, Taiwan.
authors.forename: Wan-Ling
authors.initials: WL
authors.lastname: Chang-Liao
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Hou
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Chang
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Lee
authors.forename: Yin-Meng
authors.initials: YM
authors.lastname: Tsai
authors.forename: Lie-Chwen
authors.initials: LC
authors.lastname: Lin
authors.forename: Tung-Hu
authors.initials: TH
authors.lastname: Tsai
mesh_terms: D000818:Animals; D001682:Biological Availability; D001774:Blood Chemical Analysis / Q000592:standards; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D004051:Diethylhexyl Phthalate / Q000097:blood / Q000493:pharmacokinetics*; D005243:Feces / Q000737:chemistry; D008297:Male; D010795:Phthalic Acids / Q000737:chemistry; D010968:Plasticizers / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D021241:Spectrometry, Mass, Electrospray Ionization / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D010795:Phthalic Acids; D010968:Plasticizers; D004051:Diethylhexyl Phthalate; C027561:butylbenzyl phthalate
references.citation: Regul Toxicol Pharmacol. 1999 Jun;29(3):327-57
references.pmid: 10388618
references.citation: Toxicol Appl Pharmacol. 1985 Jun 30;79(2):246-56
references.pmid: 4002226
references.citation: J Appl Toxicol. 2013 Sep;33(9):1027-35
references.pmid: 23754470
references.citation: Toxicol In Vitro. 2012 Mar;26(2):315-22
references.pmid: 22186153
references.citation: Environ Health Perspect. 1986 Mar;65:293-8
references.pmid: 3086077
references.citation: Environ Health Perspect. 1986 Mar;65:299-307
references.pmid: 3086078
references.citation: Environ Health Perspect. 1982 Nov;45:19-25
references.pmid: 7140694
references.citation: Rapid Commun Mass Spectrom. 2006;20(7):1135-43
references.pmid: 16521163
references.citation: Am J Ind Med. 2001 Jan;39(1):100-11
references.pmid: 11148020
references.citation: J Expo Sci Environ Epidemiol. 2010 Jan;20(1):38-53
references.pmid: 19127283
references.citation: Arch Toxicol. 1985 Sep;57(4):226-30
references.pmid: 4091646
references.citation: Environ Health Perspect. 2003 Feb;111(2):139-45
references.pmid: 12573895
references.citation: Toxicol Sci. 2000 Jun;55(2):433-43
references.pmid: 10828276
references.citation: Int J Pharm. 2013 Jun 25;450(1-2):36-43
references.pmid: 23618960
references.citation: Aust N Z J Psychiatry. 1975 Jun;9(2):111-3
references.pmid: 1057421
references.citation: Anal Bioanal Chem. 2003 Feb;375(4):527-33
references.pmid: 12610705
references.citation: Int J Pharm. 2011 Jun 30;412(1-2):47-51
references.pmid: 21497186
references.citation: J Chromatogr. 1985 Nov 8;344:167-75
references.pmid: 4086538
references.citation: Int J Mol Sci. 2013 Jan 04;14(1):836-49
references.pmid: 23344044
references.citation: N Engl J Med. 1975 Feb 20;292(8):381-6
references.pmid: 1110722
references.citation: J Chromatogr B Biomed Sci Appl. 2001 May 5;755(1-2):297-303
references.pmid: 11393717
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Feb 25;816(1-2):269-80
references.pmid: 15664359
references.citation: Crit Rev Toxicol. 1996 Jun;26(4):365-481
references.pmid: 8817083
references.citation: Environ Health Perspect. 1973 Jan;3:123-9
references.pmid: 4704560
references.citation: Food Chem Toxicol. 1998 Nov;36(11):963-70
references.pmid: 9771559
references.citation: Environ Health Perspect. 1986 Mar;65:279-91
references.pmid: 3709454
references.citation: Int J Androl. 2006 Feb;29(1):155-65; discussion 181-5
references.pmid: 16466535
references.citation: J Pharm Biomed Anal. 1999 Dec;21(5):923-30
references.pmid: 10703960
references.citation: Environ Health Perspect. 2001 Mar;109(3):229-37
references.pmid: 11333183
references.citation: FASEB J. 2008 Mar;22(3):659-61
references.pmid: 17942826
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2004 May 25;804(2):397-401
references.pmid: 15081935
references.citation: Arch Toxicol. 1985 Dec;58(2):72-7
references.pmid: 4091659
references.citation: AAPS J. 2007 Mar 30;9(1):E109-14
references.pmid: 17408234
references.citation: Arch Toxicol. 2005 Jul;79(7):367-76
references.pmid: 15700144
references.citation: J Pharmacokinet Biopharm. 1978 Apr;6(2):165-75
references.pmid: 671222
references.citation: Risk Anal. 2006 Jun;26(3):803-24
references.pmid: 16834635
references.citation: Environ Health Perspect. 2002 Apr;110(4):363-75
references.pmid: 11940454
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Jun 1;852(1-2):22-34
references.pmid: 17236825
references.citation: Int J Pharm. 2000 Dec 4;210(1-2):109-15
references.pmid: 11163992
references.citation: Talanta. 2008 Jan 15;74(4):498-504
references.pmid: 18371667
references.citation: Food Addit Contam. 1995 Mar-Apr;12(2):245-53
references.pmid: 7781821
references.citation: Toxicology. 1974 Mar;2(1):51-65
references.pmid: 4823738
references.citation: Drug Metab Rev. 1989;21(1):13-34
references.pmid: 2696633