Refinement of naphthalene exposure assessment in human biomonitoring based on the synthesis of naphthyl sulfate isomers and HPLC-MS analysis

Abstract Naphthalene is widely distributed in the environment, and due to its potential carcinogenicity, exposure assessment is crucial. Its metabolic marker, naphthyl sulfate, is easily detectable but exists as a mixture of isomers sulfated at the 1- and 2-positions. Determining the isomeric ratio is essential for precise exposure assessment in human biomonitoring; however, no such studies have been reported to date. In this study, these isomers were successfully synthesized using organic synthesis techniques, and their structures were elucidated via X-ray crystallographic analysis. The synthesized compounds enabled the analysis of their isomeric ratio in human urine samples using high-performance liquid chromatography-mass spectrometry. As a result, we successfully quantified the isomeric ratio of naphthyl sulfate in 37 human urine samples.