The dissociation constants of the cytostatic bosutinib by nonlinear least-squares regression of multiwavelength spectrophotometric and potentiometric pH-titration data

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216275%3A25310%2F16%3A39900232" target="_blank" >RIV/00216275:25310/16:39900232 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/abs/pii/S0731708515302715?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0731708515302715?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jpba.2015.12.012" target="_blank" >10.1016/j.jpba.2015.12.012</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The dissociation constants of the cytostatic bosutinib by nonlinear least-squares regression of multiwavelength spectrophotometric and potentiometric pH-titration data

Popis výsledku v původním jazyce

Potentiometric and spectrophotometric pH-titration of the multiprotic cytostatics bosutinib for dissociation constants determination were compared. Bosutinib treats patients with positive chronic myeloid leukemia. Bosutinib exhibits four protonatable sites in a pH range from 2 to 11, where two pK are well separated (Delta pK&gt;3), while the other two are near dissociation constants. In the neutral medium, bosutinib occurs in the slightly water soluble form LH that can be protonated to the soluble cation LH43+. The molecule LH can be dissociated to still difficultly soluble anion L-. The set of spectra upon pH from 2 to 11 in the 239.3-375.0 nm was divided into two absorption bands: the first one from 239.3 to 290.5 nm and the second from 312.3 to 375.0 nm, which differ in sensitivity of chromophores to a pH change. Estimates of pK of the entire set of spectra were compared with those of both absorption bands. Due to limited solubility of bosutinib the protonation in a mixed aqueous-methanolic medium was studied. In low methanol content of 3-6% three dissociation constants can be reliably determined with SPECFIT/32 and SQUAD(84) and after extrapolation to zero content of methanol they lead to pK(c1)=3.43(12), pK(c2)=4.54(10), pK(c3)=7.56(07) and pK(c4)=11.04(05) at 25 degrees C and pK(c1)=3.44(06), pK(c2)=5.03(08) pK(c3)=7.33(05) and pK(c4)=10.92(06) at 37 degrees C. With an increasing content of methanol in solvent the dissociation of bosutinib is suppressed and the percentage of LH32* decreases and LH prevails. From the potentiometric pH-titration at 25 degrees C the concentration dissociation constants were estimated with ESAB pK(c1)=3.51(02), pK(c2)=4.37(02), pK(c3)=7.97(02) and pK(c4)=11.05(03) and with HYPERQUAD: pK(c1)=3.29(12), pK(c2)=4.24(10), pK(c3)=7.95(07) and pK(c4)=11.29(05).

Název v anglickém jazyce

The dissociation constants of the cytostatic bosutinib by nonlinear least-squares regression of multiwavelength spectrophotometric and potentiometric pH-titration data

Popis výsledku anglicky

Potentiometric and spectrophotometric pH-titration of the multiprotic cytostatics bosutinib for dissociation constants determination were compared. Bosutinib treats patients with positive chronic myeloid leukemia. Bosutinib exhibits four protonatable sites in a pH range from 2 to 11, where two pK are well separated (Delta pK&gt;3), while the other two are near dissociation constants. In the neutral medium, bosutinib occurs in the slightly water soluble form LH that can be protonated to the soluble cation LH43+. The molecule LH can be dissociated to still difficultly soluble anion L-. The set of spectra upon pH from 2 to 11 in the 239.3-375.0 nm was divided into two absorption bands: the first one from 239.3 to 290.5 nm and the second from 312.3 to 375.0 nm, which differ in sensitivity of chromophores to a pH change. Estimates of pK of the entire set of spectra were compared with those of both absorption bands. Due to limited solubility of bosutinib the protonation in a mixed aqueous-methanolic medium was studied. In low methanol content of 3-6% three dissociation constants can be reliably determined with SPECFIT/32 and SQUAD(84) and after extrapolation to zero content of methanol they lead to pK(c1)=3.43(12), pK(c2)=4.54(10), pK(c3)=7.56(07) and pK(c4)=11.04(05) at 25 degrees C and pK(c1)=3.44(06), pK(c2)=5.03(08) pK(c3)=7.33(05) and pK(c4)=10.92(06) at 37 degrees C. With an increasing content of methanol in solvent the dissociation of bosutinib is suppressed and the percentage of LH32* decreases and LH prevails. From the potentiometric pH-titration at 25 degrees C the concentration dissociation constants were estimated with ESAB pK(c1)=3.51(02), pK(c2)=4.37(02), pK(c3)=7.97(02) and pK(c4)=11.05(03) and with HYPERQUAD: pK(c1)=3.29(12), pK(c2)=4.24(10), pK(c3)=7.95(07) and pK(c4)=11.29(05).

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10406 - Analytical chemistry

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Pharmaceutical and Biomedical Analysis

ISSN

0731-7085

e-ISSN

—

Svazek periodika

120

Číslo periodika v rámci svazku

February

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

158-167

Kód UT WoS článku

000370585700022

EID výsledku v databázi Scopus

2-s2.0-84951765576