The UHPLC-UV method applied for the forced degradation study of ixazomib and HRMS identification of its degradation products
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F23%3A10467755" target="_blank" >RIV/00179906:_____/23:10467755 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11160/23:10467755
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=3_sXzZ7.To" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=3_sXzZ7.To</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.jpba.2022.115220" target="_blank" >10.1016/j.jpba.2022.115220</a>
Alternative languages
Result language
angličtina
Original language name
The UHPLC-UV method applied for the forced degradation study of ixazomib and HRMS identification of its degradation products
Original language description
Ixazomib is the only orally active proteasome inhibitor used in clinical practice as an anticancer drug. The novel, rapid UHPLC-UV assay for ixazomib was developed and applied to the forced degradation study followed by HRMS identification of the main degradation products. Oxidative deboronation and hydrolysis of the amid bond were found to be the principal degradation pathways. The chemical standards of the main degradation products were prepared. The method was validated for the simultaneous assay of ixazomib and its degradation products within the concentration ranges of 2.50-100.00 mu g/mL (ixazomib); 0.75-60.00 mu g/mL (Impurity A and B) and 1.25-60.00 mu g/mL (Impurity C). The stability study revealed that ixazomib in solution is: 1) relatively stable in neutral and acidic environments, 2) its decomposition is accelerated at higher pH, 3) it is sensitive to the effects of oxidants and light, and 4) the degradation of ixazomib follows the first-order kinetics under neutral, acidic, alkaline, and UV stress. Contrary, the solid substance of ixazomib citrate was relatively resistant to heat (70 degrees C), heat/humidity (70 degrees C/75 % RH), and UV irradiation for 24 h. This study presents the first MS-compatible UHPLC method for the quantification of ixazomib and its degradation products. Furthermore, it provides data about the inherent stability and kinetics of degradation of ixazomib in a solution that may be useful in further investigation of this drug, or the development of novel proteasome inhibitors based on the ixazomib structure.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
<a href="/en/project/EF16_019%2F0000841" target="_blank" >EF16_019/0000841: Efficiency and safety improvement of current drugs and nutraceuticals: advanced methods - new challenges</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
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 Pharmaceutical and Biomedical Analysis
ISSN
0731-7085
e-ISSN
1873-264X
Volume of the periodical
225
Issue of the periodical within the volume
February
Country of publishing house
GB - UNITED KINGDOM
Number of pages
9
Pages from-to
115220
UT code for WoS article
000964719400001
EID of the result in the Scopus database
2-s2.0-85145986477