Xu Xu, Zhang Junfeng, Zhang Lin, Liu Weili, Weisel Clifford P
Environmental Biomarker Shared Resource, The Cancer Institute of New Jersey and Environmental and Occupational Health Science Institute, University of Medicine and Dentistry of New Jersey (UMDNJ), Piscataway, NJ 08854, USA.
Rapid Commun Mass Spectrom. 2004;18(19):2299-308. doi: 10.1002/rcm.1625.
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitously present in the environment and associated with a variety of adverse health effects. Monohydroxylated PAHs (OH-PAHs), metabolites of PAHs, have been employed as biomarkers for human exposure assessment of PAHs. This manuscript describes new, selective detection methods for OH-PAHs using liquid chromatography and tandem mass spectrometry (LC/MS/MS). Electrospray ionization was operated in the negative ion mode to detect the deprotonated PAH metabolites (M-H). Hydroxylated metabolites of naphthalene, fluorene, phenanthrene, fluoranthene, pyrene, benzo[c]phenanthrene, chrysene, benzo[a]anthracene, and benzo[a]pyrene were selected for the method development. Based on the collision-induced dissociation MS/MS spectra of the selected OH-PAHs, a characteristic ion fragmentation, loss of 28 Da from the M--H ion, was identified for all of these OH-PAHs. This characteristic fragmentation was exploited for selective screening for OH-PAHs in human urine by incorporating a constant neutral loss (CNL) scan with data-dependent scanning, using a triple quadruple mass spectrometer. Selected reaction monitoring (SRM) was also used to tentatively identify isomers of the target OH-PAHs in human urine. The excellent linearity (3-4 orders of magnitude) and signal-to-noise performance provided by the SRM method allowed development of a sensitive LC/MS/MS method for measuring OH-PAHs in urine samples. The limits of detection of the SRM method ranged from approximately 0.1-5 pg on column for a suite of OH-PAHs tested in the study. The LC-SRM method was applied, following enzymatic deconjugation and solid-phase extraction of the urine, to preliminarily determine the OH-PAH concentrations in urine specimens from six Chinese non-occupationally exposed workers and seven Chinese coke oven workers.
多环芳烃（PAHs）广泛存在于环境中，并与多种不良健康影响相关。单羟基化多环芳烃（OH-PAHs）作为PAHs的代谢产物，已被用作人类PAHs暴露评估的生物标志物。本手稿描述了使用液相色谱和串联质谱（LC/MS/MS）对OH-PAHs进行新的选择性检测方法。电喷雾电离在负离子模式下运行，以检测去质子化的PAH代谢产物（M-H）。选择萘、芴、菲、荧蒽、芘、苯并[c]菲、 Chrysene、苯并[a]蒽和苯并[a]芘的羟基化代谢产物进行方法开发。基于所选OH-PAHs的碰撞诱导解离MS/MS光谱，确定了所有这些OH-PAHs的特征性离子碎片，即M-H离子损失28 Da。通过使用三重四极杆质谱仪，将恒定中性损失（CNL）扫描与数据依赖扫描相结合，利用这种特征性碎片对人尿中的OH-PAHs进行选择性筛查。选择反应监测（SRM）也用于初步鉴定人尿中目标OH-PAHs的异构体。SRM方法提供的出色线性（3-4个数量级）和信噪比性能使得开发一种灵敏的LC/MS/MS方法来测量尿样中的OH-PAHs成为可能。在该研究中测试的一组OH-PAHs的SRM方法的检测限在柱上约为0.1-5 pg。在对尿液进行酶解结合和固相萃取后，应用LC-SRM方法初步测定了六名中国非职业暴露工人和七名中国焦炉工人尿液样本中的OH-PAH浓度。
