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Electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis of 1-Bromopropane mercapturic acid in human urine.

Authors
Cheever-KL; Marlow-KL; Stinson-D; Teass-AW; DeBord-DG
Source
Proceedings of the International Conference on Occupational and Environmental Exposures of Skin to Chemicals: Science & Policy, Arlington, VA, September 8-11, 2002. Morgantown, WV: National Institute for Occupational Safety and Health, 2002 Sep; :1-2
Link
NIOSHTIC No.
20027267
Abstract
1-Bromopropane (1-BP, CAS 106-95-5), used as an alternative solvent to chlorofluorocarbons and 1,1,1-trichloroethane, has been reported to cause reproductive and neurotoxicity in male rats. The related 2-bromopropane has been shown to cause similar toxicity in rats as well as amenorrhea, oligozoospermia, and anemia induction in workers. Although the mechanism of action of 1-BP has yet to be explained, it is thought that metabolic activation to reactive intermediates may be important. Metabolism of 1-BP is complex and is reported to occur by pathways which include debromination, oxidation by CYP2E1 and glutathione S-conjugation. 3-Bromopropionic acid and n-propanol are reported urinary metabolites of 1-BP whereas the glutathione conjugate, S-n-propyl-glutathione is further cleaved to S-n-propyl-L-cysteine and further to mercapturic acids N-acetyl-S-(n-propyl)-L-cysteine (M1), N-acetyl-S-(n-propyl)-L-cysteine-S-oxide (M2), N-acetyl-S-(2-carboxyethyl)-L-cysteine (M3), and N-acetyl-S-(3-hydroxy-n-propyl)-L-cysteine (M4). A potential biomonitoring method was developed to measure urinary levels of (M1), (M2), (M3) and (M4). The mercapturic acid standards as well as the stable isotope-labeled analog of (M1) internal standard were synthesized using the general procedure of van Bladern et al. (1980). A BenchMate« II robotic workstation was used to automate sample preparation. Bond Elute« 500 mg C18 SPE columns were conditioned with acetone, MeOH (5% HCl) and 5% MeOH in H2O pH 3. Samples were mixed with internal standard and loaded onto columns. A fraction containing >90% of 1-BP metabolites was collected in 3-mL acetone, reduced to dryness under N2 and dissolved in 1 mL MeOH for HPLC-MS/MS (ThermoQuest Finnegan LCQ tandem mass spectrometer) analysis on a 150 X 2 mm Phenomenex Aqua 3Ám C18 300A column. Chromatographic standards were chromatographed using a 10-min linear gradient H2O 1% acetic acid to MeOH 1% acetic acid at 300 microliters/min to elute the compounds of interest within 10 min. During the chromatographic run the mass spectrometer was operated in multiple segments using ESI-MS/MS, in the positive ion mode for detection of protonated (M1), (M2), (M3) and (M4) and Selected Reaction Monitoring of major transition products. Urine samples fortified with a mixture of standards were mixed with 10 micrograms/mL of internal standard and processed for evaluation of recovery, limits of detection (LOD) and limits of quantitation (LOQ). Calibration of (M1), (M2), (M3) and (M4) was linear from 30 - 10000 ng/mL (r(2)>0.99). The sample preparation and analysis appears to offer significant advantages over typical preconcentration and derivatization procedures that would be required for GC-MS analysis of these compounds. Thus, 1-BP internal exposure levels for various exposure situations can be rapidly determined by analysis of these metabolites in a single assay using a selective automated sample preparation system.
Keywords
Chemical-properties; Chemical-processing; Urinalysis; Urine-chemistry; Biomarkers; Metabolites; Exposure-assessment; Chromatographic-analysis; Analytical-chemistry; Mass-spectrometry; Analytical-methods; Analytical-processes
CAS No.
106-95-5
Publication Date
20020908
Document Type
Abstract
Fiscal Year
2002
NTIS Accession No.
NTIS Price
NIOSH Division
DART
Source Name
Proceedings of the International Conference on Occupational and Environmental Exposures of Skin to Chemicals: Science & Policy, Arlington, VA, September 8-11, 2002
State
WV; VA; OH
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