An LC-MS/MS method for quantification of HR011303, a novel highly selective urate transporter 1 inhibitor in beagle dogs and the application to a pharmacokinetic study.
Biomed Chromatogr
; 33(10): e4604, 2019 Oct.
Article
em En
| MEDLINE
| ID: mdl-31128076
ABSTRACT
HR011303 is a novel and highly selective urate transporter 1 (URAT1) inhibitor. In this study, a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantification of HR011303 in beagle dog plasma. Plasma samples were pretreated with protein-precipitation extraction by acetonitrile and added with a trifluoromethyl substituted analog of HR011303 as internal standard. The chromatographic separation was performed on a Shiseido C18 column (100 × 4.6 mm, i.d., 5 µm) by mobile phases consisting of 5 mm ammonium-formic acid (1000.1) and acetonitrile-formic acid (1000.1) solutions in gradient elution. The MS detection was conducted in electrospray positive ionization with multiple reactions monitoring at m/z 338 â 240 for HR011303 and m/z 328 â 230 for the internal standard using 25 eV argon gas collision induced dissociation. The established LC-MS/MS method showed good selectivity, sensitivity, precision and accuracy. The plasma pharmacokinetics of HR011303 in beagle dogs following both oral and intravenous administration were then successfully evaluated using this LC-MS/MS method.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cromatografia Líquida
/
Transportadores de Ânions Orgânicos
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Proteínas de Transporte de Cátions Orgânicos
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Moduladores de Transporte de Membrana
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Espectrometria de Massas em Tandem
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article