Detection and structure elucidation of the new degradation impurities in the pharmaceutical formulations of ruxolitinib hydrobromide

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F20%3A43923834" target="_blank" >RIV/60461373:22340/20:43923834 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0731708520303265?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0731708520303265?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jpba.2020.113266" target="_blank" >10.1016/j.jpba.2020.113266</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Detection and structure elucidation of the new degradation impurities in the pharmaceutical formulations of ruxolitinib hydrobromide

Popis výsledku v původním jazyce

New degradation impurities at m/z 327.15 and m/z 311.16 using gradient UHPLC method with UV detection and highly selective QDa mass detection were observed during the ruxolitinib hydrobromide (RUX.HBr) : excipient binary mixture degradation study. High mass resolution LC–MS and nuclear magnetic resonance (NMR) techniques were employed to identify and fully characterize the degradation compounds. The degradation impurities were unambiguously identified as (R)-4-amino-6-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)pyrimidine-5-carboxylic acid and (R)-3-(4-(6-amino-5-formylpyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile and mechanism of their formation was proposed. It has been confirmed that the degradation products are formed in mixtures of RUX.HBr with some excipients in the presence of oxygen. Based on the forced degradation study, the chemically stable of pharmaceutical formulations were prepared to eliminate the formation of these impurities. © 2020 Elsevier B.V.

Název v anglickém jazyce

Detection and structure elucidation of the new degradation impurities in the pharmaceutical formulations of ruxolitinib hydrobromide

Popis výsledku anglicky

New degradation impurities at m/z 327.15 and m/z 311.16 using gradient UHPLC method with UV detection and highly selective QDa mass detection were observed during the ruxolitinib hydrobromide (RUX.HBr) : excipient binary mixture degradation study. High mass resolution LC–MS and nuclear magnetic resonance (NMR) techniques were employed to identify and fully characterize the degradation compounds. The degradation impurities were unambiguously identified as (R)-4-amino-6-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)pyrimidine-5-carboxylic acid and (R)-3-(4-(6-amino-5-formylpyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile and mechanism of their formation was proposed. It has been confirmed that the degradation products are formed in mixtures of RUX.HBr with some excipients in the presence of oxygen. Based on the forced degradation study, the chemically stable of pharmaceutical formulations were prepared to eliminate the formation of these impurities. © 2020 Elsevier B.V.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10406 - Analytical chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

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

186

Číslo periodika v rámci svazku

JUL 15 2020

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

6

Strana od-do

113266

Kód UT WoS článku

000541133300051

EID výsledku v databázi Scopus

2-s2.0-85083644306