Tomoo Nakagawa

Direct determination of N-methyl-2-pyrrolidone metabolites in urine by HPLC-electrospray ionization-MS/MS using deuterium-labeled compounds as internal standard

N-methyl-2-pyrrolidone (NMP) has been used in many industries and biological monitoring of NMP exposure is preferred to atmospheric monitoring in occupational health. We developed an analytical method that did not include solid phase extraction (SPE) but utilized deuterium-labeled compounds as internal standard for high-performance liquid chromatography-electrospray ionization-mass spectrometry using a C30 column. Urinary concentrations of NMP and its known metabolites 5-hydoxy-N-methyl-2-pyrrolidone (5-HNMP), N-methyl-succinimide (MSI), and 2-hydroxy-N-methylsuccinimide (2-HMSI) were determined in a single run. The method provided baseline separation of these compounds. Their limits of detection in 10-fold diluted urine were 0.0001, 0.006, 0.008, and 0.03 mg/L, respectively. Linear calibration covered a biological exposure index (BEI) for urinary concentration. The within-run and total precisions (CV, %) were 5.6% and 9.2% for NMP, 3.4% and 4.2% for 5-HNMP, 3.7% and 6.0% for MSI, and 6.5% and 6.9% for 2-HMSI. The method was evaluated using international external quality assessment samples, and urine samples from workers exposed to NMP in an occupational area.

Analysis of phthalates in aromatic and deodorant aerosol products and evaluation of exposure risk

We established an analytical method for the detection of seven phthalates, dimethyl phthalate, diethyl phthalate (DEP), benzyl butyl phthalate, di-i-butyl phthalate, dibutyl phthalate (DBP), diethylhexyl phthalate (DEHP), and di-n-octhyl phthalate, using an ultra high performance liquid chromatograph equipped with a photodiode array detector. This method is quick, with minimal contamination, and was applied to the analysis of aromatic and deodorant aerosol products. Phthalates were detected in 15 of 52 samples purchased from 1999 to 2012 in Yokohama. Three types of phthalate (DEP, DBP, DEHP) were detected, and their concentrations ranged from 0.0085-0.23% DEP in nine samples, 0.012-0.045% DBP in four samples, and 0.012-0.033% DEHP in four samples. No other phthalate esters were detected. Furthermore, we estimated phthalate exposure via breathing in commonly used aromatic and deodorant aerosol products, then evaluated the associated risk. The estimated levels of phthalate exposure were lower than the tolerated daily limit, but the results indicated that aromatic and deodorant aerosol products could be a significant source of phthalate exposure.