Electrospray Ionization Tandem Mass Spectrometry (ESI-MS/MS) Analysis of Urinary Metabolites of 1,1, 2,2-Tetrachloroethylene Using an Automated SPE Sample Preparation System

Details

• Personal Author:
  Butler MA ; Cheever KL ; DeBord, D. Gayle ; Marlow, Kate L. ; Toraason MA
• Description:
  1,1,2,2-Tetrachloroethylene [Perchloroethylene] (PERC, CAS 127-18-4), used extensively as a dry cleaning agent and in industrial degreasing processes, has been reported to increase the incidence of liver tumors in mice or of nephrotoxicity and renal tumors in male rats. Bioactivation of PERC is reported to occur by two pathways, oxidation by CYP2E1 and glutathione S-conjugation. Trichloroacetic acid (TCA, CAS 76-03-9) and dichloroacetic acid (DCA, CAS 79-43-6) are reported urinary metabolites of PERC oxidation wherease the glutathione conjugate, S-(1,2,2-trichlorovinyl) -L-glutathione (TCVG) is further cleaved to S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC). A potential biomonitoring method was developed to measure urinary levels of TCA, DCA, TCVC and N-ac-TCVC. Stable isotope-labeled analogs of TCVC and N-ac-TCVC were prepared (Bartles and Miner, 1989) and deuterated DCA was purchased as internal standards. A BenchMate II robotic workstation was used to automate sample preparation. PERC metabolites (>90% recovery) were analyzed using a ThermoQuest Finnegan LCQ tandem mass spectrometer. Chromatographic standards TCVC and N-ac-TCVC were synthesized as above. Compounds of interest were eluted within 12 min and detected using ESI-MS/MS in multiple segments, initially in the negative ion mode for detection of TCA and DCA, and subsequently in the position ion mode for TCVC and N-ac-TCVC. Urine samples from rats exposed to 100, 500, or 1000 mg/kg PERC contained detectable amounts of PERC metabolites in urine over a 48-hr period. The LOD per injection was 30 fmol for TCVC, 800 fmol for N-ac-TCVC, 10 pmol for DCA, and 75 pmol for TCA. This procedure appears to offer significant advantages over typical extraction and derivatization methods for the same compounds by GC-MS. Thus, PERC internal dose for various exposures can be rapidly quantified using metabolites in a single assay using an automated sample preparation system. [Description provided by NIOSH]
• Subjects:
  Animals Chromatography Digestive System Digestive System Diseases Energy Metabolism Environmental Exposure Laboratories Liver Lung Diseases Occupational Health Respiratory Tract Diseases Safety Urine

  More +
• Keywords:
  Animal Studies Bioactivation Chromatographic Analysis Exposure Assessment Exposure Levels Ionization Laboratory Animals Liver Cancer Liver Disorders Liver Tumors Mass Spectrometry Metabolites Pulmonary System Disorders Respiratory System Disorders Sampling Sampling Methods Urinalysis

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DBBS - Division of Biomedical and Behavioral Sciences
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  54
• Issue:
  1
• NIOSHTIC Number:
  nn:20020904
• Citation:
  Toxicologist 2000 Mar; 54(1):207
• CAS Registry Number:
  Dichloroacetic acid (CAS RN 79-43-6) ; Tetrachloroethylene (CAS RN 127-18-4) ; Trichloroacetic acid (CAS RN 76-03-9)
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 39th Annual Meeting, March 19-23, 2000, Philadelphia, Pennsylvania
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c2fba1126f94407c093068f85d267a1a340fe661996e2b517d48667686a9c1b0cedb772d28e0d071b6e257cf41ec7623dbdf54ed36b3a268dd7e869c4bf1a729
• Download URL:
  https://stacks.cdc.gov/view/cdc/198546/cdc_198546_DS1.pdf
• File Type:
  [PDF - 301.02 KB ]