Detection of antimuscarinic agents tolterodine and fesoterodine and their metabolite 5-hydroxymethyl tolterodine by ion transfer voltammetry at a polarized room-temperature ionic liquid membrane

Ion transfer voltammetry at a polarized hydrophobic room temperature ionic liquid (RTIL) membrane was used for evaluation of the diffusion coefficients and the standard Gibbs energies of ion transfer of the protonated antimuscarinic agents tolterodine (TOL), fesoterodine (FES), and their common metabolite 5-hydroxymethyl tolterodine (5-HMT), as well as for their determination in the aqueous samples and urine. An analysis of the pH effect provided the parameters characterizing their lipophilicity both in their ionic and neutral forms confirming a remarkably low lipophilicity of 5-HMT. The application of the ion transfer voltammetry for a monitoring of the enzymatic hydrolysis of FES to 5-HMT was demonstrated. For determination of protonated TOL, FES, and 5-HMT in the aqueous samples, linear calibration dependences were plotted in the range 2.0-12.5 mu mol L-1 with the mean limit of detection (LOD) 0.43 mu mol L-1. Analogous linear calibration dependences were constructed for 10times diluted urine spiked with 2.0-12.5 mu mol L-1 TOL, FES, and 5-HMT with the mean LOD 0.65 mu mol L-1. Unfortunately, determination of 5-HMT in diluted urine samples was interfered by an unknown ionic urine component, which somewhat increased its particular LOD. (C) 2019 Elsevier Ltd. All rights reserved.