Quantitation of ortho-cresyl phosphate adducts to butyrylcholinesterase in human serum by immunomagnetic-UHPLC-MS/MS.

Autor: Johnson D; Oak Ridge Institute for Science and Education, Centers for Disease Control and Prevention, Atlanta, GA, USA., Carter MD; Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA., Crow BS; Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA., Isenberg SL; Oak Ridge Institute for Science and Education, Centers for Disease Control and Prevention, Atlanta, GA, USA., Graham LA; Oak Ridge Institute for Science and Education, Centers for Disease Control and Prevention, Atlanta, GA, USA., Erol HA; Oak Ridge Institute for Science and Education, Centers for Disease Control and Prevention, Atlanta, GA, USA., Watson CM; Oak Ridge Institute for Science and Education, Centers for Disease Control and Prevention, Atlanta, GA, USA., Pantazides BG; Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA., van der Schans MJ; The Netherlands Organization for Applied Scientific Research (TNO), Technical Sciences, CBRN Protection, Rijswijk, The Netherlands., Langenberg JP; The Netherlands Organization for Applied Scientific Research (TNO), Technical Sciences, CBRN Protection, Rijswijk, The Netherlands., Noort D; The Netherlands Organization for Applied Scientific Research (TNO), Technical Sciences, CBRN Protection, Rijswijk, The Netherlands., Blake TA; Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA., Thomas JD; Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA., Johnson RC; Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Jazyk: angličtina
Zdroj: Journal of mass spectrometry : JMS [J Mass Spectrom] 2015 Apr; Vol. 50 (4), pp. 683-92.
DOI: 10.1002/jms.3576
Abstrakt: 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.
(Published 2015. This article is a U.S. Government work and is in the public domain in the USA.)
Databáze: MEDLINE
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