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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
Author(s) -
Wang Ju,
Yao Wei,
Fan Di,
Qiu Zhenjun,
Song Jieqiong,
Pan Kai,
Hang Taijun
Publication year - 2019
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4604
Subject(s) - beagle , chemistry , pharmacokinetics , chromatography , transporter , pharmacology , biochemistry , medicine , gene
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 C 18 column (100 × 4.6 mm, i.d., 5 μm) by mobile phases consisting of 5 m m 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.