Effect of charge of quaternary ammonium cations on lipophilicity and electroanalytical parameters: Task for ion transfer voltammetry

Abstract

The electrochemical behavior of three differently charged drug molecules (zwitter-ionic acetylcarnitine, bi-cationic succinylcholine and tri-cationic gallamine) was studied at the interface between two immiscible electrolyte solutions. Tetramethylammonium was used as a model mono cationic molecule and internal reference. The charge and molecular structure were found to play an important role in the drug lipophilicity. The studied drugs gave a linear correlation between the water – octanol (logPoctanol) partition coefficients and the electrochemically measured water – 1,2-dichloroethane (logPDCE) partition coefficients. Comparison with tetraalkylammonium cations indicating that the correlation between logPoctanol and logPDCE is molecular structure dependent. The highest measured sensitivity and lowest limit of detection were found to be 0.543mA·dm3·mol−1 and 6.25μM, respectively, for the tri-cationic gallamine. The sensitivity for all studied ions was found to be a linear function of molecular charge. The dissociation constant of the carboxylic group of zwiter-ionic acetylcarnitine was calculated based on voltammetric parameters and was found to be 4.3. This study demonstrates that electrochemistry at the liquid – liquid interface is powerful technique when it comes to electroanalytical or pharmacokinetic drug assessment.