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

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.

• Authors: Karel Musil, Veronika Florianova, Pavel Bucek, Vlastimil Dohnal, Kamil Kuca, Kamil Musilek
• Journal: Journal of pharmaceutical and biomedical analysis (J Pharm Biomed Anal) Vol. 117 Pg. 240-6 (Jan 05 2016) ISSN: 1873-264X [Electronic] England
• PMID: 26386953 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Cholinesterase Reactivators
• Oximes
• Acetylcholinesterase

Topics

• Acetylcholinesterase (analysis, chemistry)
• Chemistry, Pharmaceutical (methods, standards)
• Cholinesterase Reactivators (analysis, chemistry)
• Oximes (analysis, chemistry)
• Spectrophotometry, Ultraviolet (methods, standards)
• Structure-Activity Relationship