Journal of Pharmaceutical and Biomedical Analysis 2016-01-05

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

Karel Musil, Veronika Florianova, Pavel Bucek, Vlastimil Dohnal, Kamil Kuca, Kamil Musilek

Index: J. Pharm. Biomed. Anal. 117 , 240-6, (2015)

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Abstract

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.Copyright © 2015 Elsevier B.V. All rights reserved.