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
| Autor: | Ju Wang, Taijun Hang, Kai Pan, Di Fan, Zhenjun Qiu, Wei Yao, Jieqiong Song |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Electrospray Organic Cation Transport Proteins Collision-induced dissociation Clinical Biochemistry Organic Anion Transporters Mass spectrometry Sensitivity and Specificity 030226 pharmacology & pharmacy 01 natural sciences Biochemistry Beagle Analytical Chemistry 03 medical and health sciences chemistry.chemical_compound Dogs 0302 clinical medicine Drug Stability Pharmacokinetics Tandem Mass Spectrometry Membrane Transport Modulators Drug Discovery Animals Molecular Biology Pharmacology Chromatography Trifluoromethyl Chemistry 010401 analytical chemistry Extraction (chemistry) Reproducibility of Results General Medicine 0104 chemical sciences Linear Models Female Selectivity Chromatography Liquid |
| Zdroj: | Biomedical Chromatography. 33 |
| ISSN: | 1099-0801 0269-3879 |
| Popis: | 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 (100:0.1) and acetonitrile-formic acid (100:0.1) solutions in gradient elution. The MS detection was conducted in electrospray positive ionization with multiple reactions monitoring at m/z 338 → 240 for HR011303 and m/z 328 → 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. |
| Databáze: | OpenAIRE |
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