HPLC-MS/MS를 이용한 트리클로로에틸렌 대사산물의 다중 분석법 확립
Multiple Determinations of Trichloroethylene Metabolites in a Concurrent Biological Media using High Performance Liquid Chromatography Coupled with Tandem Mass Spectrometry
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초록
Objectives: We aimed to develop a measurement method of five metabolites of trichloroethylene (TCE) in aconcurrent biological sample, e.g., trichloroacetic acid (TCA), dichloroacetic acid (DCA), S-(1,2-dichlorovinyl)glutathione (DCVG), S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and N-Acetyl-S-(1,2-dichlorovinyl)-L-cysteine(NAcDCVC) and to validate the method before application to pharmacokinetic study. Methods: TCE metabolites were simultaneously analyzed using high performance liquid chromatographycoupled with electrospray ionization mass spectrometry (HPLC-ESI-MS/MS) with as little as 50 μL of serumand urine. DCA, TCA and NAcDCVC were extracted with diethyl ether, while DCVC and DCVG wereextracted by solid phase extraction. This method was validated according to the guidelines for bioanalyticalmethod validation of the Korean National Institute of Toxicological Research. Then, we determined the fivemetabolites in five strains of mice at 24 hr after exposure to 1 g TCE /kg body weight. Results: The limits of detection for the five metabolites in biological samples ranged from 0.001 to 0.076 nmol/mL,which is comparable to or better than those previously reported. Most calibration curves showed good linearity(R2=0.99), and between-batch variation was less than 20% expressing acceptable robustness and reproducibility. Using this method, we found TCA and DCA were detected in all test mice at 24 hr after the oral administrationwhile NAcDCVC and DCVC were detected in some strains, which showed strain-dependent metabolism ofTCE. Conclusions: The present method could provide robust and accurate measurements of major key metabolites ofTCE in biological media, which allowed concurrent analysis of TCE metabolism for limited amounts of biospecimens.
Abstract
Objectives: We aimed to develop a measurement method of five metabolites of trichloroethylene (TCE) in aconcurrent biological sample, e.g., trichloroacetic acid (TCA), dichloroacetic acid (DCA), S-(1,2-dichlorovinyl)glutathione (DCVG), S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and N-Acetyl-S-(1,2-dichlorovinyl)-L-cysteine(NAcDCVC) and to validate the method before application to pharmacokinetic study. Methods: TCE metabolites were simultaneously analyzed using high performance liquid chromatographycoupled with electrospray ionization mass spectrometry (HPLC-ESI-MS/MS) with as little as 50 μL of serumand urine. DCA, TCA and NAcDCVC were extracted with diethyl ether, while DCVC and DCVG wereextracted by solid phase extraction. This method was validated according to the guidelines for bioanalyticalmethod validation of the Korean National Institute of Toxicological Research. Then, we determined the fivemetabolites in five strains of mice at 24 hr after exposure to 1 g TCE /kg body weight. Results: The limits of detection for the five metabolites in biological samples ranged from 0.001 to 0.076 nmol/mL,which is comparable to or better than those previously reported. Most calibration curves showed good linearity(R2=0.99), and between-batch variation was less than 20% expressing acceptable robustness and reproducibility. Using this method, we found TCA and DCA were detected in all test mice at 24 hr after the oral administrationwhile NAcDCVC and DCVC were detected in some strains, which showed strain-dependent metabolism ofTCE. Conclusions: The present method could provide robust and accurate measurements of major key metabolites ofTCE in biological media, which allowed concurrent analysis of TCE metabolism for limited amounts of biospecimens.
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