Analysis of Human Placental Tissues Using Gas Chromatography High Resolution Accurate Mass Spectrometry to Characterize Exposure to a Range of Semivolatile Organic Compounds

Measuring chemical exposures during fetal development is critical to understanding the environmental influences on chronic disease risk. The placenta, in direct contact with the fetus throughout gestation, offers a vital matrix for assessing fetal chemical exposures. However, analytical challenges remain due to its heterogeneous composition and the need to detect trace levels of diverse chemical classes. This study aimed to develop and validate a robust analytical method to quantify and screen for environmental contaminants in human placental tissue using QuEChERS-based extraction that was optimized for high recovery and reproducibility while minimizing matrix interference. Analysis was performed using gas chromatography–high resolution mass spectrometry (GC-HRMS) with isotope dilution for targeted quantitation of 119 semivolatile organic compounds (SVOCs). Method performance was assessed using spiked placental samples and a NIST-certified reference material. The validated method was applied to 50 placental samples collected from a North Carolina pregnancy cohort (Project HOPE 1000). The optimized method displayed acceptable recoveries (50–150%) for up to 75% of target analytes across four spike levels ranging from 0.1 to 10 ng/g wet weight (ww). A total of 72 compounds were detected in at least one placental sample, including several brominated flame retardants, organophosphate esters, polychlorinated biphenyls, pesticides, polycyclic aromatic hydrocarbons, and phthalates. This validated GC-HRMS method effectively quantifies a broad range of environmental contaminants in placental tissue while balancing throughput, sensitivity, and versatility and can be used to support exposome research in pregnancy cohorts.