A round robin approach to the analysis of bisphenol a (BPA) in human blood samples

Abstract

BackgroundHuman exposure to bisphenol A (BPA) is ubiquitous, yet there are concerns about whether BPA can be measured in human blood. This Round Robin was designed to address this concern through three goals: 1) to identify collection materials, reagents and detection apparatuses that do not contribute BPA to serum; 2) to identify sensitive and precise methods to accurately measure unconjugated BPA (uBPA) and BPA-glucuronide (BPA-G), a metabolite, in serum; and 3) to evaluate whether inadvertent hydrolysis of BPA-G occurs during sample handling and processing.MethodsFour laboratories participated in this Round Robin. Laboratories screened materials to identify BPA contamination in collection and analysis materials. Serum was spiked with concentrations of uBPA and/or BPA-G ranging from 0.09-19.5 (uBPA) and 0.5-32 (BPA-G) ng/mL. Additional samples were preserved unspiked as ‘environmental’ samples. Blinded samples were provided to laboratories that used LC/MSMS to simultaneously quantify uBPA and BPA-G. To determine whether inadvertent hydrolysis of BPA metabolites occurred, samples spiked with only BPA-G were analyzed for the presence of uBPA. Finally, three laboratories compared direct and indirect methods of quantifying BPA-G.ResultsWe identified collection materials and reagents that did not introduce BPA contamination. In the blinded spiked sample analysis, all laboratories were able to distinguish low from high values of uBPA and BPA-G, for the whole spiked sample range and for those samples spiked with the three lowest concentrations (0.5-3.1 ng/ml). By completion of the Round Robin, three laboratories had verified methods for the analysis of uBPA and two verified for the analysis of BPA-G (verification determined by: 4 of 5 samples within 20% of spiked concentrations). In the analysis of BPA-G only spiked samples, all laboratories reported BPA-G was the majority of BPA detected (92.2 – 100%). Finally, laboratories were more likely to be verified using direct methods than indirect ones using enzymatic hydrolysis.ConclusionsSensitive and accurate methods for the direct quantification of uBPA and BPA-G were developed in multiple laboratories and can be used for the analysis of human serum samples. BPA contamination can be controlled during sample collection and inadvertent hydrolysis of BPA conjugates can be avoided during sample handling.

Serum bisphenol A as a predictor of chronic kidney disease progression in primary hypertension

“…As serum BPA in a relative low range is high enough to elicit biological effects through its related receptors, assessing serum BPA rather than urinary BPA is reasonable and should not be ignored [29,30]. On the other hand, BPA determined after enzymatic hydrolysis by a sensitive and selective liquid chromatography-tandem mass spectrometry method is thought to be the most accurate chemistry method [6]. A significant correlation (r ¼ 0.971) was confirmed between the BPA values measured by the ELISA and the high-performance liquid chromatography [31].…”

“…However, as circulating BPA is considered to be more directly related to its biological effects, measurement of circulating BPA is needed [6,29]. National Institute of Environmental Health Sciences has demonstrated that serum BPA can be accurately assayed [6]. As serum BPA in a relative low range is high enough to elicit biological effects through its related receptors, assessing serum BPA rather than urinary BPA is reasonable and should not be ignored [29,30].…”

“…BPA levels in the urine are up to 3-250 times higher than in the serum, with a mean of 42-fold [28], the serum BPA concentration might underestimate the actual body burden of BPA in our population. However, as circulating BPA is considered to be more directly related to its biological effects, measurement of circulating BPA is needed [6,29]. National Institute of Environmental Health Sciences has demonstrated that serum BPA can be accurately assayed [6].…”

“…BPA is widely used in the manufacturing of polycarbonate plastics and epoxy resins; therefore, BPA is present in human daily necessities such as food and beverage containers and dental sealants [4]. Epidemiological studies have suggested that BPA could have many effects on human health [6]. Exposure to BPA has been shown to be associated with cardiovascular diseases such as coronary artery disease [7] and peripheral arterial disease [8].…”

The role of human biological monitoring in health risk assessment

“…Analysis of samples must be carried out with fully validated analytical methods and supported by the use of quality control samples (Albertini et al, 2006;Calafat and Needham 2008;Smolders et al, 2009). Finally, the laboratory should participate in inter-laboratory exercise as and when available (Göen et al, 2012;Schindleret al, 2014;Vandenberg et al, 2014).…”