JOURNAL OF THE CZECH PHARMACEUTICAL SOCIETY AND THE SLOVAK PHARMACEUTICAL SOCIETY

Čes. slov. farm. 2012, 61(1):44-52

Analytical profile of mono[{3-[4-(2-ethoxyethoxy)-benzoyloxy]-2-hydroxypropyl}-tert-butylammonium] fumarate

Ivan Malík1,*, Lenka Mitterová1, Fils Andriamainty1, Petr Mokrý2, Miloš Lukáč3, Jozef Csöllei2, Jana Gališinová1, Janka Karlovská4
1 Katedra farmaceutickej chémie, Farmaceutická fakulta Univerzity Komenského
2 Ústav chemických léčiv, Farmaceutická fakulta, Veterinární a farmaceutická univerzita Brno
3 Katedra chemickej teórie liečiv, Farmaceutická fakulta, Univerzita Komenského v Bratislave
4 Laboratórium NMR, Farmaceutická fakulta, Univerzita Komenského v Bratislave

The present paper aims at a complex spectral and physicochemical evaluation of mono[{3-[4-(2-ethoxyethoxy)-benzoyloxy]-2-hydroxypropyl}-tert-butylammonium] fumarate, the potential ultra-short acting blocker of ß1-adrenergic receptors. The identity of the evaluated compound (labelled as UPB-2) was confirmed by 1H-, 13C-NMR and IR spectral data as well. The estimated physicochemical parameters included melting point data, solubility in various media, purity checking (adsorption thin-layer chromatography), surface activity determination (non--direct Traube stalagmometric method), acidobasic characteristics (pKa value determination by alkalimetric titration), log ε values estimation (spectrophotometrically in UV/VIS region) and a study of the influence of acidic and alkaline media towards the stability of UPB-2. Other experimentally estimated values were lipohydrophilic descriptors using RP-HPLC (log k') and the log Pexps in various lipohydrophilic media by the shake flask method. Based on the log Pexp readouts, the ability to permeate across the brain-blood barrier was predicted. For the content determination of UBP-2 the RP-HPLC (reversed-phase HPLC), the method of an internal standard and UV/VIS spectrophotometry at the wavelength of 260 nm (aqueous medium) and at 258 nm (methanolic medium) was applied.

Keywords: ß1-blockers; analytical evaluation; spectral and physicochemical properties; content determination

Received: August 25, 2011; Accepted: October 17, 2011; Published: January 1, 2012  Show citation

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Malík I, Mitterová L, Andriamainty F, Mokrý P, Lukáč M, Csöllei J, et al.. Analytical profile of mono[{3-[4-(2-ethoxyethoxy)-benzoyloxy]-2-hydroxypropyl}-tert-butylammonium] fumarate. Čes. slov. farm. 2012;61(1-2):44-52.
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