Osaka Occupational Health Service Center, Japan Industrial Safety and Health Association, Japan.
Department of Forensic Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan.
J Occup Health. 2019 Jan;61(1):82-90. doi: 10.1002/1348-9585.12026.
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.
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).
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.
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.
本研究旨在建立一种简单、准确的气相色谱-质谱（GC-MS）法，同时测定甲苯的马尿酸（HA）、二甲苯的甲基马尿酸（MHA）以及苯乙烯或乙苯的扁桃酸（MA）和苯乙醇酸（PGA）这四种有机溶剂的四种尿代谢物。
采用 2,2-二甲氧基丙烷将四种代谢物直接甲酯化，并用 GC-MS 进行分析。根据美国食品药品监督管理局的指导，对所提议的方法进行了验证。通过分析职业医学 ClinChek-控制（RECIPE Chemicals + Instruments GmbH）来确认该方法的准确性。
校准曲线显示每种代谢物在 10-1000mg/L 浓度范围内具有线性关系，相关系数均大于 0.999。对于每种代谢物，检测限和定量限分别为 3mg/L 和 10mg/L。回收率为 93%-117%，日内准确度（以偏离名义值表示）为 92.7%-103.0%，日内精密度（以相对标准偏差表示）为 1.3%-4.7%。日间准确度和精密度分别为 93.4%-104.0%和 1.2%-9.5%。使用所提议的方法获得的 ClinChek 分析值足够准确。
该方法简单准确，适用于职业性接触四种有机溶剂的生物监测的常规分析。
