The Thermodynamic Overlapping pKa of the Antitumor Drug Ibrutinib Using Multiwavelength UV/VIS-Spectroscopy and Potentiometry
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
The Thermodynamic Overlapping pKa of the Antitumor Drug Ibrutinib Using Multiwavelength UV/VIS-Spectroscopy and Potentiometry
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>ost</sub> - Miscellaneous article in a specialist periodical
CEP classification
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OECD FORD branch
10403 - Physical chemistry
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Analytical & Pharmaceutical Research
ISSN
2473-0831
e-ISSN
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Volume of the periodical
6
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
1-10
UT code for WoS article
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EID of the result in the Scopus database
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