Direct methyl esterification with 2,2-dimethoxypropane for the simultaneous determination of urinary metabolites of toluene, xylene, styrene, and ethylbenzene by gas chromatography-mass spectrometry.

OBJECTIVES: The purpose of this study was to develop a simple and accurate gas chromatography-mass spectrometry (GC-MS) method for simultaneous determination of four urinary metabolites from four organic solvents, that is, hippuric acid (HA) from toluene, methylhippuric acid (MHA) from xylene, and mandelic acid (MA) and phenylglyoxylic acid (PGA) from styrene or ethylbenzene for biological monitoring. METHODS: The four metabolites were directly methyl-esterified with 2,2-dimethoxypropane and analyzed using GC-MS. The proposed method was validated according to the US Food and Drug Administration guidance. The accuracy of the proposed method was confirmed by analyzing a ClinChek® -Control for occupational medicine (RECIPE Chemicals +Instruments GmbH). RESULTS: Calibration curves showed linearity in the concentration range of 10-1000 mg/L for each metabolite, with correlation coefficients >0.999. For each metabolite, the limits of detection and quantification were 3 mg/L and 10 mg/L, respectively. The recovery was 93%-117%, intraday accuracy, expressed as the deviation from the nominal value, was 92.7%-103.0%, and intraday precision, expressed as the relative standard deviation (RSD), was 1.3%-4.7%. Interday accuracy and precision were 93.4%-104.0% and 1.2%-9.5%, respectively. The analytical values of ClinChek obtained using the proposed method were sufficiently accurate. CONCLUSIONS: The proposed method is a simple and accurate which is suitable for routine analyses that could be used for biological monitoring of occupational exposure to four organic solvents.

Evaluation of urinary cyclohexanediols and cyclohexanol as biomarkers of occupational exposure to cyclohexane.

OBJECTIVES: The aim of the present study was to comparatively evaluate the usefulness of urinary cyclohexanediols (CHdiols-U) and cyclohexanol (CHol-U) as biomarkers of occupational exposure to cyclohexane (CH). METHODS: Sixteen subjects (14 men and 2 women) were exposed to CH during proof-printing work. Personal exposure monitoring was conducted during the whole shift on the last working day of the week. The time-weighted average level of exposure to CH (CH-A) was measured using a diffusive sampler. Two urine samples were collected from each worker at different times during the same week: a baseline urine sample (before the first shift of the working week, after a 5-day holiday with no CH exposure) and an end-of-shift urine sample (after the last shift of the same working week, the same day personal exposure monitoring was conducted). CH-A, CHdiols-U and CHol-U were determined using a gas chromatograph-flame ionization detector. RESULTS: The CH-A concentrations ranged from 4.5 to 60.3 ppm, with a geometric mean (GM) of 18.1 ppm. The GMs and ranges (in parenthesis) of the creatinine (cr)-corrected end-of-shift 1,2-CHdiol-U, 1,4-CHdiol-U and CHol-U concentrations were 12.1 (4.1-36.6), 7.5 (2.4-20.1) and 0.4 (0.2-1.0) mg/g cr, respectively. Both CHdiols-U at the end of the shift were significantly correlated with CH-A (correlation coefficients for 1,2-CHdiol-U and 1,4-CHdiol-U of 0.852 and 0.847, respectively). No correlation was observed between CH-A and CHol-U. CONCLUSIONS: CHdiols-U at the end of the last shift of the working week are suitable biomarkers of occupational exposure to CH, but CHol-U is not suitable.

A method for routine analysis of urinary 4,4'-methylenebis (2-chloroaniline) by gas chromatography-electron capture detection.

OBJECTIVES: The purpose of this study was to develop a simple and cost-effective method for the determination of urinary 4,4'-methylenebis (2-chloroaniline) (MBOCA) by gas chromatography-electron capture detection (GC-ECD) for biological monitoring of occupational exposure to MBOCA. METHODS: MBOCA was prepared by liquid-liquid extraction after alkaline hydrolysis, derivatized with N-methyl-bis (trifluoroacetamide) and then analyzed using GC-ECD. The proposed method was validated in accordance with the US Food and Drug Administration guidance. RESULTS: The calibration curve showed linearity in the range 1-100 µg/l, with a correlation coefficient of >0.999. The limits of detection and quantification were 0.3 µg/l and 1 µg/l, respectively. The recovery was 94-99%. Intraday accuracy, expressed as the deviation from the nominal value, was 90.5-100.3%, and intraday precision, expressed as the relative standard deviation, was 0.3-2.4%. Interday accuracy and precision were 87.8-100.2% and 0.3-4.1%, respectively. CONCLUSIONS: The proposed method is a simple and cost-effective method suitable for routine analyses and could be useful for biological monitoring of occupational exposure to MBOCA.