Identification and Quantification of 1-Hydroxybutene-2-yl Mercapturic Acid in Human Urine by UPLC- HILIC-MS/MS as a Novel Biomarker for 1,3-Butadiene Exposure

Abstract

1,3-Butadiene (BD) is a Class 1 carcinogen present at workplaces, in polluted air, in automobile exhaust, and in tobacco smoke. 2-Hydroxybutene-1-yl mercapturic acid (2-MHBMA) is a urinary metabolite often measured as a biomarker for exposure to BD. Here, we show for the first time that an additional MHBMA isomer is present at significant amounts in human urine, 1-hydroxybutene-2-yl mercapturic acid (1-MHBMA). For its quantification, a highly sensitive UPLC-HILIC-MS/MS method was developed and validated. Analyzing urinary samples of 183 volunteers, we demonstrate that 1-MHBMA is a novel and potentially more reliable biomarker for BD exposure than the commonly analyzed 2-MHBMA.

Analysis of 18 urinary mercapturic acids by two high-throughput multiplex-LC-MS/MS methods

“…Moreover, our data confirm recent findings showing significant differences between smokers and non-smokers for AAMA [22], GAMA [34], 2-HPMA [22], 3-HPMA [22], AMCC [22], CEMA [21], SPMA [7], HMPMA [33], and 1-/2-MHBMA [24]. In accordance with the literature, for DHBMA, similar concentrations in smokers and nonsmokers were observed [21,27].…”

“…Although numerous methods for the quantification of different MAs by LC-MS/MS have been reported in the recent past, the majority of those assays target a rather small set of up to six MAs [8,17,[20][21][22][24][25][26]. In addition, many of these methods lack the capability of quantifying MAs from environmental exposures in low levels.…”

High throughput HPLC–ESI−-MS/MS methodology for mercapturic acid metabolites of 1,3-butadiene: Biomarkers of exposure and bioactivation

“…4;6 The availability of sensitive, robust, high throughput methodologies for monitoring human exposure to butadiene (BD) is essential for molecular epidemiology studies of human cancer risk and susceptibility. Although multiple HPLC-ESI − MS/MS methods have been previously described for quantification of BD-mercapturic acids in humans (Table S-1), 23–25;27–32 many of these methods require at least 0.5 ml of urine, and thus are not applicable to studies where the sample volume is limited (< 0.2 ml). Furthermore, large epidemiological studies typically involve hundreds or even thousands of human subjects, necessitating high throughput analytical strategies.…”

“…26 Several mass spectrometry-based methods have been developed for quantification of MHBMA and DHBMA in human urine. 20;23–25;27–32 However, many of these methods require a large sample volume (> 0.5 ml) and are not amenable to high throughput analysis (Table S-1). …”

Study of urinary 2-{[2-(acetylamino-2-carboxyethyl]sulfanyl}butanedioic acid, a mercapturic acid of rats treated with maleic acid

“…The half life of urinary MAMA is longer than that of urinary MA, suggesting that MAMA is suitable to serve as a biomarker for current MA exposure. Previous studies in styrene (Seutter-Berlage et al, 1978), 1,2-diethylbenzene (Linhart et al, 1996), 1,3-butadiene (Kotapati et al, 2011;Sterz et al, 2012), 1,2,4-trimethylbeneze (Tsujimoto et al, 2000), 2-chloroprene (Eckert et al, 2013), allyl chloride (De Rooij et al, 1996), acrylonitrile (Kedderis et al, 1993), and acrylamide (Sumner et al, 1992) have demonstrated that mercapturic acids are the major detoxification products and the biomarkers of exposure. Our results also reveal that the MA exposure can lead to the formation of MAMA in rat urine, which suggests that MA could be potentially detoxified through GSH conjugation in vivo and excreted through urine.…”