Details:

Alternative Title:
J Mass Spectrom
Personal Author:
Johnson, Darryl ; Carter, Melissa D. ; Crow, Brian S. ; Isenberg, Samantha L. ; Graham, Leigh Ann ; ... More +
Johnson, Darryl ; Carter, Melissa D. ; Crow, Brian S. ; Isenberg, Samantha L. ; Graham, Leigh Ann ; Erol, H. Akin ; Watson, Caroline M. ; Pantazides, Brooke G. ; van der Schans, Marcel J. ; Langenberg, Jan P. ; Noort, Daan ; Blake, Thomas A. ; Thomas, Jerry D. ; Johnson, Rudolph C. Less -
Description:
Tri-ortho-cresyl phosphate (ToCP) is an anti-wear, flame retardant additive used in industrial lubricants, hydraulic fluids and gasoline. The neurotoxic effects of ToCP arise from the liver-activated metabolite 2-(o-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (cresyl saligenin phosphate or CBDP), which inhibits esterase enzymes including butyrylcholinesterase (BChE). Following BChE adduction, CBDP undergoes hydrolysis to form the aged adduct ortho-cresyl phosphoserine (oCP-BChE), thus providing a biomarker of CBDP exposure. Previous studies have identified ToCP in aircraft cabin and cockpit air, but assessing human exposure has been hampered by the lack of a laboratory assay to confirm exposure. This work presents the development of an immunomagnetic-UHPLC-MS/MS method for the quantitation of unadducted BChE and the long-term CBDP biomarker, oCP-BChE, in human serum. The method has a reportable range from 2.0 ng/ml to 150 ng/ml, which is consistent with the sensitivity of methods used to detect organophosphorus nerve agent protein adducts. The assay demonstrated high intraday and interday accuracy (≥85%) and precision (RSD ≤ 15%) across the calibration range. The method was developed for future analyses of potential human exposure to CBDP. Analysis of human serum inhibited in vitro with CBDP demonstrated that the oCP-BChE adduct was stable for at least 72 h at 4, 22 and 37 °C. Compared to a previously reported assay, this method requires 75% less sample volume, reduces analysis time by a factor of 20 and demonstrates a threefold improvement in sensitivity. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Subject:
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Butyrylcholinesterase
Chromatography, High Pressure Liquid
Humans
Immunomagnetic Separation
Limit Of Detection
Reproducibility Of Results
Tandem Mass Spectrometry
Tritolyl Phosphates

Source:
J Mass Spectrom. 50(4):683-692
Pubmed ID:
26149113
Pubmed Central ID:
PMC5713888
Document Type:
Journal Article
Funding:
CC999999/Intramural CDC HHS/United States
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:146b6983fb86cacaa3c467a6a65e3cb0646f49e5c9576ecfae6e76e200c4556f
File Type:

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