JOURNAL OF THE CZECH PHARMACEUTICAL SOCIETY AND THE SLOVAK PHARMACEUTICAL SOCIETY

Čes. slov. farm. 2011, 60(2):84-93

Analytical evaluation of mono[{3-[4-(2-etoxyetoxy)-benzoyloxy]-2-hydroxypropyl}-isopropyl-ammonium]fumarate

Ivan Malík1,*, Fils Andriamainty1, Eva Sedlárová1, Jozef Čižmárik1, Jana Gališinová1, Petr Mokrý2, Jozef Csöllei2, Janka Karlovská3, Miloš Lukáč4
1 Univerzita Komenského v Bratislave, Farmaceutická fakulta, Katedra farmaceutickej chémie
2 Veterinární a farmaceutická univerzita v Brně, Farmaceutická fakulta, Ústav chemických léčiv
3 Univerzita Komenského v Bratislave, Farmaceutická fakulta, Laboratórium NMR
4 Univerzita Komenského v Bratislave, Farmaceutická fakulta, Katedra chemickej teórie liečiv

The present paper deals with a complex spectral and physicochemical evaluation of mono[{3-[4--(2-etoxyetoxy)-benzoyloxy]-2-hydroxypropyl}-isopropylammonium]fumarate, a potential ultra-short acting ß1-blocker. The identity of the substance under study (labelled as UPB-1) was confirmed by 1H- and 13C-NMR spectra as well as IR spectrometry. The determined fundamental physicochemical characteristics included the determination of the melting point, solubility in a spectrum of solvents, verification of purity (adsorption thin-layer chromatography), determination of surface activity (Traube's stalagmometric method), acidobasic characteristics (pKa value by means of alkalimetric titration), determination of log ε values using spectrophotometry in UV/VIS region, as well as the evaluation of the effect of acid and basic media on the stability of the substance under the study. Other experimentally determined parameters were lipohydrophilic characteristics essayed by means of RP-HPLC (log k'), and the shake-flask method was employed to determine the values of the partition coefficients Pexp (resp. log Pexp) in different lipohydrophilic media. On the basis of log Pexp- data, the ability of the substance to penetrate the hematoencephalic barrier was predicted. To determine the UPB-1 content, RP-HPLC (reversed-phase HPLC) method of the internal standard and UV/VIS spectrophotometry at the wavelength of 260 nm (aqueous medium) and 258 nm (methanol medium) were used.

Keywords: ß1-blockers; analytic evaluation; spectral and physicochemical characte-ristic; content determinbation

Received: January 13, 2011; Accepted: February 23, 2011; Published: February 1, 2011  Show citation

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Malík I, Andriamainty F, Sedlárová E, Čižmárik J, Gališinová J, Mokrý P, et al.. Analytical evaluation of mono[{3-[4-(2-etoxyetoxy)-benzoyloxy]-2-hydroxypropyl}-isopropyl-ammonium]fumarate. Čes. slov. farm. 2011;60(2):84-93.
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