High throughput HPLC–ESI−-MS/MS methodology for mercapturic acid metabolites of 1, 3-butadiene: Biomarkers of exposure and bioactivation. (5th November 2015)

• Record Type: Journal Article
• Authors: Kotapati, Srikanth; Esades, Amanda; Matter, Brock; Le, Chap; Tretyakova, Natalia
• Is Part Of: Chemico-biological interactions. Volume 241(2015)
• Page Start: 23
• Page End: 31
• Publication Date: 2015-11-05
• Subjects: BD 1, 3-butadiene -- EB 3, 4-epoxy-1-butene -- HMVK hydroxymethyl vinyl ketone -- EBD 3, 4-epoxy-1, 2-diol -- DEB 1, 2, 3, 4-diepoxybutane -- MHBMA monohydroxybutenyl mercapturic acid -- DHBMA dihydroxybutyl mercapturic acid -- THBMA trihydroxybutyl mercapturic acid -- THB-Val 1, 2, 3-trihydroxybutyl-valine -- Pyr-Val N, N-(2, 3-dihydroxy-1, 4-butadiyl)-valine -- EH epoxide hydrolase -- GST glutathione S-transferase -- HPLC-ESI−-MS/MS high performance liquid chromatography-electrospray ionization tandem mass spectrometry -- SPE solid phase extraction -- LOD limit of detection -- LOQ limit of quantification; 1, 3-Butadiene -- Urinary metabolites -- Occupational exposure -- Metabolism -- Quantitative analysis; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2015.02.009
• Languages: English
• ISSNs: 0009-2797

Abstract

Graphical abstract: Highlights: New HPLC–ESI − -MS/MS method was developed for urinary metabolites of 1, 3-butadiene. BD-mercapturic acids were quantified in occupationally exposed workers and controls. BD-mercapturic acid levels were increased in BD exposed workers. Urinary BD-mercapturic acids were associated with BD-hemoglobin adducts in blood. Abstract: 1, 3-Butadiene (BD) is an important industrial and environmental carcinogen present in cigarette smoke, automobile exhaust, and urban air. The major urinary metabolites of BD in humans are 2-( N -acetyl-l -cystein-S-yl)-1-hydroxybut-3-ene/1-( N -acetyl-l -cystein-S-yl)-2-hydroxybut-3-ene (MHBMA), 4-( N -acetyl-l -cystein-S-yl)-1, 2-dihydroxybutane (DHBMA), and 4-( N -acetyl-l -cystein-S-yl)-1, 2, 3-trihydroxybutyl mercapturic acid (THBMA), which are formed from the electrophilic metabolites of BD, 3, 4-epoxy-1-butene (EB), hydroxymethyl vinyl ketone (HMVK), and 3, 4-epoxy-1, 2-diol (EBD), respectively. In the present work, a sensitive high-throughput HPLC–ESI – -MS/MS method was developed for simultaneous quantification of MHBMA and DHBMA in small volumes of human urine (200 μl). The method employs a 96 well Oasis HLB SPE enrichment step, followed by isotope dilution HPLC–ESI − -MS/MS analysis on a triple quadrupole mass spectrometer. The validated method was used to quantify MHBMA and DHBMA in urine of workers from a BD monomer and styrene-butadiene rubber production facility (40 controls and 32 occupationally exposed to BD). Urinary THBMA concentrations were also determined in the same samples. The concentrations of all three BD-mercapturic acids and the metabolic ratio (MHBMA/(MHBMA + DHBMA + THBMA)) were significantly higher in the occupationally exposed group as compared to controls and correlated with BD exposure, with each other, and with BD-hemoglobin biomarkers. This improved high throughput methodology for MHBMA and DHBMA will be useful for future epidemiological studies in smokers and occupationally exposed workers.