LC-MS/MS를 이용한 인체시료 중 프탈레이트 대사체 동시분석법 확립
Development and Validation of an On-line Column Switching HPLC-MS/MS Method for 10 Phthalate Metabolites in Human Urine
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Phthalates, such as di (2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP), which have been shown to be teratogenic and disruptive of the endocrine system are 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 urine was developed based on a switching system with an on-line pretreatment column using HPLC-MS/MS. This method was validated according to the guidelines for bioanalytical method validation of the National Institute of Toxicological Research. The limits of the detection range were between 0.2 and 0.9 ng/ml for the 10 phthalate metabolites. The calibration curves showed linearity in the range of 0.997~0.999, and the results of the intra- and interday validations were in range from 0.4 to 14.7% RSD and from 0.3 to 9.4% RSD, respectively. Recovery of the phthalate metabolites varied from 87.0 to 116.1%. This analytical method exhibited a high degree of accuracy and stable precision for all of the metabolites, and appears to be suitable for the biomonitoring of phthalates in human urine.
Abstract
Phthalates, such as di (2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP), which have been shown to be teratogenic and disruptive of the endocrine system are 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 urine was developed based on a switching system with an on-line pretreatment column using HPLC-MS/MS. This method was validated according to the guidelines for bioanalytical method validation of the National Institute of Toxicological Research. The limits of the detection range were between 0.2 and 0.9 ng/ml for the 10 phthalate metabolites. The calibration curves showed linearity in the range of 0.997~0.999, and the results of the intra- and interday validations were in range from 0.4 to 14.7% RSD and from 0.3 to 9.4% RSD, respectively. Recovery of the phthalate metabolites varied from 87.0 to 116.1%. This analytical method exhibited a high degree of accuracy and stable precision for all of the metabolites, and appears to be suitable for the biomonitoring of phthalates in human urine.
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