The Thermodynamic Overlapping pKa of the Antitumor Drug Ibrutinib Using Multiwavelength UV/VIS-Spectroscopy and Potentiometry
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216275%3A25310%2F17%3A39910711" target="_blank" >RIV/00216275:25310/17:39910711 - isvavai.cz</a>
Výsledek na webu
<a href="http://dx.doi.org/10.15406/japlr.2017.06.00173" target="_blank" >http://dx.doi.org/10.15406/japlr.2017.06.00173</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.15406/japlr.2017.06.00173" target="_blank" >10.15406/japlr.2017.06.00173</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
The Thermodynamic Overlapping pKa of the Antitumor Drug Ibrutinib Using Multiwavelength UV/VIS-Spectroscopy and Potentiometry
Popis výsledku v původním jazyce
Potentiometric and spectrophotometric pH-titrations of the antitumor drug Ibrutinib for dissociation constants determination were compared. Ibrutinib is targeting B-cell malignancies, for treatment of chronic lymphocytic leukemia, and Waldenström’s macroglobulinemia. Chemometrics approach to the nonlinear regression of the pH-spectra (REACTLAB, SQUAD84) and pH-titration (ESAB) determines four dissociation constants. Ibrutinib exhibits four protonatable centers in a pH range of 2 to 10, where only two pK are well separated (ΔpK > 3), while the others are near dissociation constants of overlapping equilibria. The molecule LH2 can protonate to sparingly soluble cations LH3+ and LH42+ and dissociate to anions LH- and L2-. The set of spectra for pH from 2 to 11 in 220 to 300nm exhibits chromophore sensitivity to a pH change. Since pH above 10 and pH below 5 occurs in a titrated solution of a very fine precipitate of Ibrutinib, this part of the potentiometric titration curve pH over 10 and pH below 5 did not undergo regression analysis to estimate pKa´s. Depending on ionic strength the thermodynamic dissociation constants were estimated at 25°C and 37°C: pKa1T = 3.22 and 3.22, pKa2T = 4.17 and 5.21, pKa3T = 6.77 and 6.77, pKa4T = 9.82 and 9.81.
Název v anglickém jazyce
The Thermodynamic Overlapping pKa of the Antitumor Drug Ibrutinib Using Multiwavelength UV/VIS-Spectroscopy and Potentiometry
Popis výsledku anglicky
Potentiometric and spectrophotometric pH-titrations of the antitumor drug Ibrutinib for dissociation constants determination were compared. Ibrutinib is targeting B-cell malignancies, for treatment of chronic lymphocytic leukemia, and Waldenström’s macroglobulinemia. Chemometrics approach to the nonlinear regression of the pH-spectra (REACTLAB, SQUAD84) and pH-titration (ESAB) determines four dissociation constants. Ibrutinib exhibits four protonatable centers in a pH range of 2 to 10, where only two pK are well separated (ΔpK > 3), while the others are near dissociation constants of overlapping equilibria. The molecule LH2 can protonate to sparingly soluble cations LH3+ and LH42+ and dissociate to anions LH- and L2-. The set of spectra for pH from 2 to 11 in 220 to 300nm exhibits chromophore sensitivity to a pH change. Since pH above 10 and pH below 5 occurs in a titrated solution of a very fine precipitate of Ibrutinib, this part of the potentiometric titration curve pH over 10 and pH below 5 did not undergo regression analysis to estimate pKa´s. Depending on ionic strength the thermodynamic dissociation constants were estimated at 25°C and 37°C: pKa1T = 3.22 and 3.22, pKa2T = 4.17 and 5.21, pKa3T = 6.77 and 6.77, pKa4T = 9.82 and 9.81.
Klasifikace
Druh
J<sub>ost</sub> - Ostatní články v recenzovaných periodicích
CEP obor
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OECD FORD obor
10403 - Physical chemistry
Návaznosti výsledku
Projekt
—
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2017
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Journal of Analytical & Pharmaceutical Research
ISSN
2473-0831
e-ISSN
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Svazek periodika
6
Číslo periodika v rámci svazku
2
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
10
Strana od-do
1-10
Kód UT WoS článku
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EID výsledku v databázi Scopus
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