The UHPLC-UV method applied for the forced degradation study of ixazomib and HRMS identification of its degradation products

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216208:11160/23:10467755

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

The UHPLC-UV method applied for the forced degradation study of ixazomib and HRMS identification of its degradation products

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

The UHPLC-UV method applied for the forced degradation study of ixazomib and HRMS identification of its degradation products

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/EF16_019%2F0000841" target="_blank" >EF16_019/0000841: Zvýšení účinnosti a bezpečnosti léčiv a nutraceutik: moderní metody - nové výzvy</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

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

1873-264X

Svazek periodika

225

Číslo periodika v rámci svazku

February

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

115220

Kód UT WoS článku

000964719400001

EID výsledku v databázi Scopus

2-s2.0-85145986477