A liquid chromatographic-mass spectrometric method to evaluate the distribution kinetics of 1,2-diethylbenzene and its metabolite 1,2-diacetylbenzene in the F344 male rat

Diethylbenzene (DEB) is a moderately volatile, colorless liquid found in gasoline, kerosene, and fuel oils. Exposure to DEB has been shown to produce peripheral neuropathy in rats, and the ortho isomer of DEB (1,2-DEB) is generally believed to be the isomer responsible. 1,2-DEB is assumed to be metabolized primarily by direct oxidation of the ethyl side chain to form two enantiomers of 1-(2-ethylphenol) ethanol and their glucuroconjugates, which are the main 1,2-DEB metabolites, and 1,2-diacetylbenzene (1,2-DAB), a minor metabolite. The metabolite 1,2-DAB appears to be a chromogenic neurotoxin. A liquid chromatographic-mass spectrometric (LC-MS) method using atmospheric pressure photoionization (APPI) for quantifying 1,2-DEB and 1,2-DAB in blood, urine, and brain tissues from animals treated with an intraperitoneal injection of 1,2-DEB was developed. Calibration curves were prepared using matrix-specific standards with concentrations ranging from 0.068 to 402 microM. Results indicate that the concentration of 1,2-DEB in blood peaked at 2 h post intraperitoneal injection and rapidly declined thereafter. In contrast, 1,2-DAB levels in blood were fairly constant up to 24 h postinjection. Urine concentrations of 1,2-DEB were highest at the first collection interval (0-12 h postinjection), and dropped rapidly thereafter; concentrations at 24 h were similar to concentrations observed at 48 h postexposure. Urine concentrations of 1,2-DAB, however, showed the reverse, with peak concentrations observed at 24 h postinjection and only a slight decrease in concentration by 48 h.