Advances in microspeciation of drugs and biomolecules: Species-specific concentrations, acid-base properties and related parameters

Károly Mazák, B. Noszál

Research output: Contribution to journalArticle

13 Citations (Scopus)


The pharmacokinetic and pharmacodynamic behaviour of drugs and the interacting biomolecules are highly influenced by their species-specific physico-chemical properties. The first of such bio-relevant, structure-dependent properties were the species-specific acid-base constants and the co-dependent concentrations, but the past decade brought significant advances to previously uncharted territories, including the experimental determination of species-specific partition coefficients, solubilities and redox equilibrium constants.This review gives an overview of the types and definitions of species-specific physico-chemical and analytical properties. We survey the pertinent literature, the fundamental relationships, and summarize some of our recent work that enabled the determination of species-specific partition coefficients for coexisting, inseparable protonation isomers and pH-independent, microscopic redox equilibrium constants.The thorough insight provided by these species-specific properties improves our understanding of the submolecular mechanism of pharmacokinetic processes. As a result, there are some pieces of clear-cut evidence of practical significance. A few of them are as follows:. - passive diffusion into lipophilic media is not necessarily predominated by the non-charged species, contrary to the widespread misbelief.- the reactive microspecies in structure-controlled, highly specific biochemical reactions is not necessarily the major one.- a preventive defence system against oxidative stress can be based upon thiol-disulfide equilibria of custom-tailored redox potentials.

Original languageEnglish
JournalJournal of Pharmaceutical and Biomedical Analysis
Publication statusAccepted/In press - Feb 28 2016



  • Acid-base chemistry
  • Amphoteric compounds
  • Concentration of microspecies
  • Lipophilicity
  • Membrane penetration
  • Microspeciation
  • Partition coefficient
  • Redox equilibria
  • Solubility
  • Species-specific physico-chemical properties
  • Zwitterions

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Spectroscopy
  • Clinical Biochemistry

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