Effect of Organic Solvent Composition on Dissociation Constants of Some Reversible Acetylcholinesterase Inhibitors

Daldal Y. D., ÇUBUK DEMİRALAY E., ÖZKAN S. A.

JOURNAL OF THE BRAZILIAN CHEMICAL SOCIETY, vol.27, no.3, pp.493-499, 2016 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 27 Issue: 3
  • Publication Date: 2016
  • Doi Number: 10.5935/0103-5053.20150276
  • Journal Name: JOURNAL OF THE BRAZILIAN CHEMICAL SOCIETY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.493-499
  • Keywords: reversible acetylcholinesterase inhibitors, dissociation constant, nonlinear regression, polarity parameter, RPLC, PHASE LIQUID-CHROMATOGRAPHY, ALZHEIMERS-DISEASE, MOBILE-PHASE, BASIC DRUGS, RETENTION, PK(A), BEHAVIOR, PH, PREDICTION
  • Ankara University Affiliated: Yes

Abstract

Reversible acetylcholinesterase inhibitors are an important group of drug compounds that are used medicinally to treat Alzheimer's disease. In this study, dissociation constant values (pK(a)) of some reversible acetylcholinesterase inhibitors (donepezil, rivastigmine and galantamine) having different functional groups were determined in different percentages of acetonitrile (MeCN)-water and methanol (MeOH)-water binary mixtures using reversed phase liquid chromatography (RPLC) method. In this way, a complete description of the retention behavior of each solute in the space defined by the pH and organic modifier percentages variables was obtained. The linear relationships established between retention factors of the species and the polarity parameter of the mobile phase (E-T(N)) was proved to predict accurately retention in liquid chromatography (LC) as a function of the acetonitrile and methanol content. In result, the estimated aqueous pK(a) values of studied basic compounds were assessed by comparing them with literature data.