- Volume 36 Issue 6
DOI QR Code
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
- Hong, Soon-Keun ;
- Nam, Hye-Seon ;
- Jung, Ki-Kyung ;
- Kang, Il-Hyun ;
- Kim, Tae-Sung ;
- Cho, Sang-Eun ;
- Jung, Su-Hee ;
- Lee, Jang-Woo ;
- Kim, Jun-Cheol ;
- Kho, Young-Lim ;
- Kang, Tae-Seok
- Received : 2010.10.13
- Accepted : 2010.12.24
- Published : 2010.12.30
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.
phthalate metabolites;on-line column switching;LC-MS/MS;biomonitoring
- 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
- 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.
- 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
- 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
- Agency for Toxic Substances and Disease Registry : Toxicological profile for di(2-ethylhexyl)phthalate (DEHP). Agency for Toxic Substances and Disease Registry, 2008.
- 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
- Gray, T. J. and Gangolli, S. D. : Aspects of the testicular toxicity of phthalate esters. Environmental Health Perspectives, 65, 229-235, 1986.
- 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.
- 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
- David, R. M. : Exposure to phthalate esters. Environmental Health Perspectives, 108, A440, 2000.
- 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
- 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
- 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
- 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
- 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
- Midwest Research Institute : Single and repeated oral dose pharmacokinetics of 14 C-labelled diisononyl phthalate with cover letter. Midwest Research Institute, 1983.
- 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
- 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.
- 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
- 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
- National Institute of Technological Research : Bioanalytical Method Validation. National Institute of Technological Research, 2002.
- 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
- US Food and Drug Administration : Bioanalytical Method Validation. Food and Drug Administration, 2001.