Analytical evaluation of mono[{3-[4-(2-etoxyetoxy)-benzoyloxy]-2-hydroxypropyl}-isopropyl-ammonium]fumarate
Authors:
Ivan Malík 1; Fils Andriamainty 1; Eva Sedlárová 1; Jozef Čižmárik 1; Jana Gališinová 1; Petr Mokrý 2; Jozef Csöllei 2; Janka Karlovská 3; Miloš Lukáč 4
Authors‘ workplace:
Univerzita Komenského v Bratislave, Farmaceutická fakulta, Katedra farmaceutickej chémie
1; Veterinární a farmaceutická univerzita v Brně, Farmaceutická fakulta, Ústav chemických léčiv
2; Univerzita Komenského v Bratislave, Farmaceutická fakulta, Laboratórium NMR
3; Univerzita Komenského v Bratislave, Farmaceutická fakulta, Katedra chemickej teórie liečiv
4
Published in:
Čes. slov. Farm., 2011; 60, 84-93
Category:
Original Articles
Overview
The present paper deals with a complex spectral and physicochemical evaluation of mono[{3-[4--(2-etoxyetoxy)-benzoyloxy]-2-hydroxypropyl}-isopropylammonium]fumarate, a potential ultrashort 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.
Key words:
ß1-blockers – analytic evaluation – spectral and physicochemical characteristic – content determinbation
Sources
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Pharmacy Clinical pharmacologyArticle was published in
Czech and Slovak Pharmacy
2011 Issue 2
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