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A two-step gas chromatography-tandem mass spectrometry method for measurement of multiple environmental pollutants in human plasma.

ABSTRACT: Individuals are exposed to a wide variety of chemicals over their lifetime, yet current understanding of mixture toxicology is still limited. We present a two-step analytical method using a gas chromatograph-triple quadrupole mass spectrometer that requires less than 1 mL of sample. The method is applied to 183 plasma samples from a study population of children with autism spectrum disorder, their parents, and unrelated neurotypical children. We selected 156 environmental chemical compounds and ruled out chemicals with detection rates less than 20% of our study cohort (n = 61), as well as ones not amenable to the selected extraction and analytical methods (n = 34). The targeted method then focused on remaining chemicals (n = 61) plus 8 additional polychlorinated biphenyls (PCBs). Persistent pollutants, such as p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and PCB congeners 118 and 180, were detected at high frequencies and several previously unreported chemicals, including 2,4,6-trichlorophenol, isosafrole, and hexachlorobutadiene, were frequently detected in our study cohort. This work highlights the benefits of employing a multi-step analytical method in exposure studies and demonstrates the efficacy of such methods for reporting novel information on previously unstudied pollutant exposures.

SUBMITTER: Johnson CL

PROVIDER: S-EPMC7790997 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Nitromethane is a volatile organic compound categorized as a Group 2B carcinogen by the International Agency for Research on Cancer. It has been detected in mainstream cigarette smoke, but few reliable methods have been reported for accurate quantification. We developed, a sensitive, selective, fully validated method for the targeted determination of nitromethane in mainstream tobacco smoke in ten U.S. domestic brands and two quality control materials (3R4F and CM6). The vapor phase portion of machine-generated cigarette mainstream smoke, under modified ISO 3308:2000 regime (ISO) and modified intense regime (HCI), from single cigarettes was collected using airtight polyvinylfluoride sampling bags. The bags' contents were extracted using methanol containing an isotopically labeled internal standard followed by gas chromatography-tandem mass spectrometry. This approach is sufficiently sensitive to measure nitromethane levels in the nanogram range, with a method limit of detection of 72.3 ng/cig. Within-product variability estimated from the replicate analysis of 10 products ranged from 4.6%-16.3% (n = 6) over the two different smoking regimes, and method reproducibility estimated from two products used as quality control materials (3R4F and CM6) yielded intermediate precision values ranging from 16.6 to 20.8% (n = 20). Under HCI, nitromethane yields in machine-generated cigarette smoke from ten different domestic cigarette products ranged from 3.2 to 12 μg/cig; under ISO yields ranged from 1.6 to 4.9 μg/cig under standardized smoking machine conditions. Nitromethane yields are related to both the smoke regime (blocking of vent holes, puff duration and puff volume) and the heterogeneity of tobacco mixtures. This method provides a selective and fully validated technique to accurately quantify nitromethane in mainstream cigarette smoke, with minimal waste generation. It is an improvement over previous methods with regards to specificity, throughput, and simplicity of the sample collection process.

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A two-step gas chromatography-tandem mass spectrometry method for measurement of multiple environmental pollutants in human plasma.

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