Chang Yan, Nguyen Charlene, Paranjpe Vikram Rajesh, Gilliland Frank, Zhang Junfeng Jim
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Nicholas School of the Environment, and Duke Global Health Institute, Duke University, Durham, NC 27708-0328, USA.
J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Aug 15;965:33-8. doi: 10.1016/j.jchromb.2014.06.005. Epub 2014 Jun 18.
Due to its cytotoxicity, genotoxicity, and adipogenicity observed in in vitro studies, bisphenol A diglycidyl ether (BADGE) may pose a health risk to humans. Quantifying BADGE exposure is an essential step to assess potential health risks associated with this ubiquitous compound widely used in certain plastic products. Due to the lack of endogenous sources for BADGE, bio-monitoring of BADGE and/or its hydrolytic metabolites (BADGE·H2O and BADGE·2H2O) can be a useful means to measure exposure. In this study, we developed a highly specific and sensitive method to measure BADGE, BADGE·H2O and BADGE·2H2O in plasma and urine, using a fast liquid-liquid extraction technique followed by a high-performance liquid chromatography and positive electrospray tandem mass spectrometry (LC-ESI-MS/MS) method. The method can quantify BADGE, BADGE·H2O and BADGE·2H2O with lower limits of quantification (LLOQ) of 0.05, 0.05 and 0.2 ng/ml, respectively. The percentage deviation of mean calculated concentrations from target concentrations was within 20%, variations across repeated analyses were within 15%, and mean extraction recovery was higher than 51.4% for all the three analytes in both plasma and urine matrices. The method has been applied to venous blood samples, cord blood samples, and urine samples collected from 9 to 14 adult volunteers. Results showed that concentrations of BADGE were lower than LLOQ in all of these samples except one urine sample. Low levels of BADGE·H2O from 0.108 to 0.222 ng/ml were observed in four venous blood samples and one urine sample (0.187 ng/ml). In contrast, concentrations of BADGE·2H2O were higher than LLOQ, varying from 0.660 to 303.593 ng/ml, in all the 10 venous blood samples and 1 cord blood sample (0.592 ng/ml) and two urine samples (0.200 and 0.306 ng/ml). The results suggest that bio-monitoring of blood and urine for BADGE exposure should focus on the hydrolysis derivatives of BADGE, mainly in the form of BADGE·2H2O.
由于在体外研究中观察到双酚A二缩水甘油醚（BADGE）具有细胞毒性、遗传毒性和成脂性，它可能对人类健康构成风险。量化BADGE暴露是评估与这种广泛用于某些塑料制品的普遍存在的化合物相关的潜在健康风险的重要一步。由于BADGE缺乏内源性来源，对BADGE及其水解代谢产物（BADGE·H2O和BADGE·2H2O）进行生物监测可以作为测量暴露的一种有用方法。在本研究中，我们开发了一种高度特异且灵敏的方法，用于测量血浆和尿液中的BADGE、BADGE·H2O和BADGE·2H2O，该方法采用快速液液萃取技术，随后是高效液相色谱和正电喷雾串联质谱（LC-ESI-MS/MS）方法。该方法能够分别以0.05、0.05和0.2 ng/ml的定量下限（LLOQ）对BADGE、BADGE·H2O和BADGE·2H2O进行定量。计算得到的平均浓度与目标浓度的百分比偏差在20%以内，重复分析的变异在15%以内，血浆和尿液基质中所有三种分析物的平均萃取回收率均高于51.4%。该方法已应用于从9至14名成年志愿者采集的静脉血样本、脐带血样本及尿液样本。结果显示，除一份尿液样本外所有这些样本中BADGE的浓度均低于LLOQ。在四份静脉血样本和一份尿液样本（0.187 ng/ml）中观察到低水平的BADGE·H2O，范围为0.108至0.222 ng/ml。相比之下，在所有10份静脉血样本、1份脐带血样本（0.592 ng/ml）和两份尿液样本（0.200和0.306 ng/ml）中，BADGE·2H2O的浓度高于LLOQ，范围为0.660至303.593 ng/ml。结果表明，对BADGE暴露进行血液和尿液生物监测应关注BADGE的水解衍生物，主要以BADGE·2H2O的形式。
