title: 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.affiliation: 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.
authors.forename: Karel
authors.initials: K
authors.lastname: Musil
authors.affiliation: University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, Hradec Kralove 50003, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Florianova
authors.affiliation: University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, Hradec Kralove 50003, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Bucek
authors.affiliation: University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, Hradec Kralove 50003, Czech Republic.
authors.forename: Vlastimil
authors.initials: V
authors.lastname: Dohnal
authors.affiliation: 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.
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
authors.affiliation: 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.
authors.forename: Kamil
authors.initials: K
authors.lastname: Musilek
mesh_terms: D000110:Acetylcholinesterase / Q000032:analysis* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000592:standards*; D002801:Cholinesterase Reactivators / Q000032:analysis* / Q000737:chemistry; D010091:Oximes / Q000032:analysis* / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet / Q000379:methods / Q000592:standards; D013329:Structure-Activity Relationship
chemical_list: D002801:Cholinesterase Reactivators; D010091:Oximes; D000110:Acetylcholinesterase
keywords: FIA/UV–vis; Organophosphate; Oxime; Reactivator; UV–vis; pK(a)