Analytical Power of LLE-HPLC-PDA-MS/MS in Drug Metabolism Studies: Identification of New Nabumetone Metabolites

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216275%3A25310%2F13%3A39896453" target="_blank" >RIV/00216275:25310/13:39896453 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11160/13:10145888

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S0731708513001167" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0731708513001167</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jpba.2013.03.006" target="_blank" >10.1016/j.jpba.2013.03.006</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Analytical Power of LLE-HPLC-PDA-MS/MS in Drug Metabolism Studies: Identification of New Nabumetone Metabolites

Popis výsledku v původním jazyce

Following oral administration, nabumetone is converted in the liver to 6-methoxy-2-naphthylacetic acid (6-MNA), the principal metabolite responsible for the NSAID effect. In this study, a new, as yet unreported phase 1 metabolite was discovered within the evaluation of nabumetone metabolism by human and rat liver microsomal fractions. Extracts from the biomatrices were subjected to chiral LLE-HPLC-PDA and achiral LLE-UHPLC-MS/MS analyses to elucidate the chemical structure of this metabolite. UHPLC-MS/MS experiments detected the presence of a structure corresponding to elemental composition C15H16O3, which was tentatively assigned as a hydroxylated nabumetone. Identical nabumetone and HO-nabumetone UV spectra obtained from the FDA detector ruled out the presence of the hydroxy group in the aromatic moiety of nabumetone. Hence, the most likely structure of the new metabolite was 4-(6-methoxy-2-naphthyl)-3-hydroxybutan-2-one (3-hydroxy nabumetone). To confirm this structure, the standard

Název v anglickém jazyce

Analytical Power of LLE-HPLC-PDA-MS/MS in Drug Metabolism Studies: Identification of New Nabumetone Metabolites

Popis výsledku anglicky

Following oral administration, nabumetone is converted in the liver to 6-methoxy-2-naphthylacetic acid (6-MNA), the principal metabolite responsible for the NSAID effect. In this study, a new, as yet unreported phase 1 metabolite was discovered within the evaluation of nabumetone metabolism by human and rat liver microsomal fractions. Extracts from the biomatrices were subjected to chiral LLE-HPLC-PDA and achiral LLE-UHPLC-MS/MS analyses to elucidate the chemical structure of this metabolite. UHPLC-MS/MS experiments detected the presence of a structure corresponding to elemental composition C15H16O3, which was tentatively assigned as a hydroxylated nabumetone. Identical nabumetone and HO-nabumetone UV spectra obtained from the FDA detector ruled out the presence of the hydroxy group in the aromatic moiety of nabumetone. Hence, the most likely structure of the new metabolite was 4-(6-methoxy-2-naphthyl)-3-hydroxybutan-2-one (3-hydroxy nabumetone). To confirm this structure, the standard

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CB - Analytická chemie, separace

OECD FORD obor

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Projekt

<a href="/cs/project/GAP207%2F10%2F2048" target="_blank" >GAP207/10/2048: Chirální chinazolinové alkaloidy: Potenciální prototypy nových antiastmatik a organokatalyzátorů</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2013

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

80

Číslo periodika v rámci svazku

červen

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

164-172

Kód UT WoS článku

000318748900021

EID výsledku v databázi Scopus

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