Determination of 1,3-Diphenylguanidine, 1,3-Di-o-tolylguanidine, and 1,2,3-Triphenylguanidine in Human Urine Using Liquid Chromatography-Tandem Mass Spectrometry

[Image: see text] 1,3-Diphenylguanidine (DPG), 1,3-di-o-tolylguanidine (DTG), and 1,2,3-triphenylguanidine (TPG) are rubber additives widely present in the indoor environment. Nevertheless, little is known about their human exposure. We developed a method for the quantification of DPG, DTG, and TPG in human urine, using high-performance liquid chromatography-tandem mass spectrometry. The quantitative analysis of target analytes at parts-per-trillion levels in urine was optimized using hydrophilic–lipophilic balanced solid-phase extraction and isotopic dilution. The method limits of detection and quantification were in the range of 0.002–0.02 and 0.005–0.05 ng/mL, respectively. The recoveries of all analytes in human urine fortified at 1, 5, 10, and 20 ng/mL concentrations were in the range of 75.3–111%, with standard deviations of 0.7–4%. The repeated measurement of similarly fortified human urine yielded intra-day and inter-day variations of 0.47–3.90 and 0.66–3.76%, respectively. The validated method was applied in the measurement of DPG, DTG, and TPG in real human urine samples, which revealed the occurrence of DPG in children’s urine samples (n = 15) with a detection frequency of 73% and at a median concentration of 0.05 ng/mL. DPG was found in 20% of adults’ urine samples (n = 20).