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Development and validation of a FIA/UV-vis method for pK(a) determination of oxime based acetylcholinesterase reactivators

K. Musil, V. Florianova, P. Bucek, V. Dohnal, K. Kuca, K. Musilek,

. 2016 ; 117 (-) : 240-6. [pub] 20150911

Language English Country England, Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't, Validation Study

Acetylcholinesterase reactivators (oximes) are compounds used for antidotal treatment in case of organophosphorus poisoning. The dissociation constants (pK(a1)) of ten standard or promising acetylcholinesterase reactivators were determined by ultraviolet absorption spectrometry. Two methods of spectra measurement (UV-vis spectrometry, FIA/UV-vis) were applied and compared. The soft and hard models for calculation of pK(a1) values were performed. The pK(a1) values were recommended in the range 7.00-8.35, where at least 10% of oximate anion is available for organophosphate reactivation. All tested oximes were found to have pK(a1) in this range. The FIA/UV-vis method provided rapid sample throughput, low sample consumption, high sensitivity and precision compared to standard UV-vis method. The hard calculation model was proposed as more accurate for pK(a1) calculation.

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$a Acetylcholinesterase reactivators (oximes) are compounds used for antidotal treatment in case of organophosphorus poisoning. The dissociation constants (pK(a1)) of ten standard or promising acetylcholinesterase reactivators were determined by ultraviolet absorption spectrometry. Two methods of spectra measurement (UV-vis spectrometry, FIA/UV-vis) were applied and compared. The soft and hard models for calculation of pK(a1) values were performed. The pK(a1) values were recommended in the range 7.00-8.35, where at least 10% of oximate anion is available for organophosphate reactivation. All tested oximes were found to have pK(a1) in this range. The FIA/UV-vis method provided rapid sample throughput, low sample consumption, high sensitivity and precision compared to standard UV-vis method. The hard calculation model was proposed as more accurate for pK(a1) calculation.
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$a Dohnal, Vlastimil $u University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, Hradec Kralove 50003, Czech Republic.
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$a Kuca, Kamil $u University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, Hradec Kralove 50003, Czech Republic; University Hospital, Biomedical Research Center, Sokolska 581, Hradec Kralove 50005, Czech Republic.
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$a Musilek, Kamil $u University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, Hradec Kralove 50003, Czech Republic; University Hospital, Biomedical Research Center, Sokolska 581, Hradec Kralove 50005, Czech Republic. Electronic address: kamil.musilek@gmail.com.
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