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In this study, we developed a highly sensitive, robust method for determining 12 congeners of two to ten chlorinated polychlorinated biphenyls (PCBs) in serum samples using gas chromatography (GC)–mass spectrometry (MS) operating in selected ion monitoring mode (SIM: m/z 35) with negative ion chemical ionization (NICI), and the results were compared with those from GC coupled with high-resolution MS (HRMS) with electron impact (EI). The recovery rates of the surrogate PCB congeners were 97.2%–112% (coefficient of variation: 5.3%–8.5%), and the method detection limits for PCBs in each matrix obtained by GC–NICI–quadrupole mass spectrometry (qMS) were 1.9–20 pg g−1 wet wt. The analytical values of the target compounds in the samples analyzed by GC–NICI–qMS and GC–EI–HRMS were comparable (Passing–Bablok regression: R = 0.888–0.967), and the analytical values obtained via GC–NICI–qMS were almost comparable with those of the certified serum samples from National Institute of Standards and Technology (NIST: SRM1957), indicating that GC–NICI–qMS is suitable for the analysis of tetra- to hepta-chlorinated PCBs in serum samples.
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