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

J Pharm Biomed Anal. 2016 Jan 5:117:240-6. doi: 10.1016/j.jpba.2015.09.010. Epub 2015 Sep 11.

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.

Keywords: FIA/UV–vis; Organophosphate; Oxime; Reactivator; UV–vis; pK(a).

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

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

Substances

  • Cholinesterase Reactivators
  • Oximes
  • Acetylcholinesterase