Journal of Environmental Health Sciences (한국환경보건학회지)

Korean Society of Environmental Health (한국환경보건학회)
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Development and Validation of On-line Column Switching HPLC-MS/MS Method for 10 Phthalate Metabolites in Human Urine

LC-MS/MS를 이용한 인체시료 중 프탈레이트 대사체 동시분석법 확립

  • Received : 2010.10.13
  • Accepted : 2010.12.24
  • Published : 2010.12.30
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Abstract

Phthalates, such as di (2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) have been proved to be teratogenics and endocrine disruptors, metabolized rapidly and excreted in the urine. In this study, a simultaneous analytical method for 10 phthalate metabolites, MnBP, MiBP, MBzP, MCHP, MEHP, MEHHP, MEOHP, MnOP, MiNP and MiDP, in human urines, based on switching system with on-line pretreatment column using HPLC-MS/MS has been developed. This method was validated according to the guideline of bioanalytical method validation of National Institute of Toxicological Research. Limits of detection range between 0.2 and 0.9 ng/ml for 10 phthalate metabolites. The calibration curves showed linearity in the range 0.997~0.999, and the results of the intra- and inter-day validations were in the range from 0.4 to 14.7% RSD and from 0.3 to 9.4% RSD, respectively. Recoveries of phthalate metabolites varied from 87.0 to 116.1%. This analytical method showed high accuracy and stable precision for all metabolites, and seems to be suitable for biomonitoring of phthalates in human urine.

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References

  1. Wensing, M., Uhde, E. and Satthammer, T. : Plastics additives in the indoor environment-frame retardants and plasticizers. Science of the Total Environment, 339, 19-40, 2005. https://doi.org/10.1016/j.scitotenv.2004.10.028
  2. US Environmental Protection Agency : An exposure and risk assessment for phthalate ester : Di(2-ethylhexyl) phthalate, di-n-butyl phthalate, dimethyl phthalete, diethyl phthalate, di-n-octyl phthalate, butyl benzyl phthalate. U.S. Environmental Protection Agency, 1981.
  3. Doull, J., Cattley, R., Elcombe, C., Lake, B. G., Swenberg, J., Wilkinson, C., Williams, G. and van Gemert, M. : A cancer risk assessment of di(2-ethylhexyl) phthalate: application of the new US EPA Risk Assessment Guidelines. Regulatory Toxicology and Pharmacology, 29, 327-357, 1999. https://doi.org/10.1006/rtph.1999.1296
  4. Tyl, R. W., Myers, C. B., Marr, M. C., Fail, P. A., Seely, J. C., Brine, D. R., Barter, R. A. and Butala, J. H. : Reproductive toxicity evaluation of dietary butyl benzyl phthalate (BBP) in rats. Reproductive Toxicology, 18, 241-264, 2004. https://doi.org/10.1016/j.reprotox.2003.10.006
  5. Agency for Toxic Substances and Disease Registry : Toxicological profile for di(2-ethylhexyl)phthalate (DEHP). Agency for Toxic Substances and Disease Registry, 2008.
  6. Kamrin, M. A. : Phthalate risks, phthalate regulation, and public health : A review. Journal of Toxicology and Environmental Health, 12, 157-174, 2009. https://doi.org/10.1080/10937400902729226
  7. Gray, T. J. and Gangolli, S. D. : Aspects of the testicular toxicity of phthalate esters. Environmental Health Perspectives, 65, 229-235, 1986.
  8. Hashizume, K., Nanya, J., Toda, C., Yasui, T., Nagano, H. and Kojima, N. : Phthalate esters detected in various water samples and biodegaration of the phthalates by microbes isolated from river water. BioPhrm Bulletin, 2, 209-214, 2002.
  9. Kluwe, W. M. : Overview of phthalate ester pharmacokinetics in mammalian species. Environmental Health Perspectives, 45, 3-9, 1982. https://doi.org/10.1289/ehp.82453
  10. David, R. M. : Exposure to phthalate esters. Environmental Health Perspectives, 108, A440, 2000.
  11. Wittassek, M. and Angerer, J. : Phthalates : metabolism and exposure, International Journal of Andrology, 31, 131-138, 2008. https://doi.org/10.1111/j.1365-2605.2007.00837.x
  12. Koch, H. M., Bolt, H. M., Preuss, R., Angerer, J. : New metabolites of di(2-ethylhexyl)phthalate (DEHP) in human urine and serum after single oral doses of deuteriumlabelled DEHP. Archives of Toxicology, 79, 367-376, 2005. https://doi.org/10.1007/s00204-004-0642-4
  13. Albro, P. W. and Moore, B. : Identification of the metabolites of simple phthalate diesters in rat urine. Journal of Chromatography A, 94, 209-218, 1974. https://doi.org/10.1016/S0021-9673(01)92368-4
  14. Leeder, J. S. and Kearns, G. L. : Pharmacogenetics in pediatrics : Implications for practice. Pediatric Clinics of North America, 44, 55-77, 1997. https://doi.org/10.1016/S0031-3955(05)70463-6
  15. Anderson, W., Castle, L. and Scotter, M. : A biomarker approach to measuring human dietary exposure to certain phthalate diesters. Food Additives and Contaminants, 18, 1068-1074, 2001. https://doi.org/10.1080/02652030110050113
  16. Midwest Research Institute : Single and repeated oral dose pharmacokinetics of 14 C-labelled diisononyl phthalate with cover letter. Midwest Research Institute, 1983.
  17. Kato, K., Silva, M. J., Wolf, C., Gray, L. E., Needham, L. L. and Calafat, A. M. : Urinary metabolites of diisodecyl phthalate in rats. Toxicology, 236, 114-122, 2007. https://doi.org/10.1016/j.tox.2007.04.009
  18. Center for Disease Contral and Prevention : Third National Report on Human Exposure to Environmental Chemicals. Department of Health and Human Services, Centers for Disease Control and Prevention, 2005.
  19. Wittasseka, M., Wiesmllerc, G., A., Koch, H., M., Eckard, R., Dobler, L., Mllera, J., Angerera, J. and Schlterb, C. : Internal phthalate exposure over the last two decades - A retrospective human biomonitoring study. International Journal of Hygiene and. Environmental Health, 210, 319-333, 2007. https://doi.org/10.1016/j.ijheh.2007.01.037
  20. Kho, Y. L., Jeoung, J. Y., Choi, K. H. and Kim P. G. : Determination of Phthalate Metabolites in Korean Children's Urine by High Performance Liquid Chromatography with Triple Quadrupole Tandem Mass Spectrometry. Journal of Environmental Health Sciences, 34, 207-278, 2008. https://doi.org/10.5668/JEHS.2008.34.3.207
  21. National Institute of Technological Research : Bioanalytical Method Validation. National Institute of Technological Research, 2002.
  22. Silva, M. J., Malek, N. A., Hodge, C. C., Reidy, J. A., Kato, K., Barr, D. B., Needham, L. L. and Brock, J. W. : Improved quntitative detection of 11 uninary phthalate metabolites in humans using liquid chromatography- atmospheric pressure chemical ionization tandem mass spectrometry. Journal of Chromatography B, 789, 393-404, 2003. https://doi.org/10.1016/S1570-0232(03)00164-8
  23. US Food and Drug Administration : Bioanalytical Method Validation. Food and Drug Administration, 2001.