Determination of lesinurad in rat plasma by a UHPLC–MS/MS assay

Abstract

Lesinurad is an oral inhibitor of urate-anion exchanger transporter 1 and has been approved by the US Food and Drug Administration for combination therapy with a xanthine oxidase inhibitor for the treatment of hyperuricemia associated with refractory gout. In the present study, a sensitive and specific ultra high-performance liquid chromatography with tandem mass spectrometry assay was established and verified for the determination of lesinurad in rat plasma and was described in details for the first time. Chromatographic separation of lesinurad and diazepam (internal standard, IS) was performed on a Rapid Resolution HT C18 column (3.0 × 100 mm, 1.8 µm) using methanol–water (70:30, v/v) as the mobile phase at a flow rate of 0.3 mL/min. Lesinurad and IS were extracted from plasma by liquid–liquid extraction using ethyl acetate. The mass spectrometric detection was carried out using an electrospray ionization source in positive mode. Multiple reaction monitoring was used for quantification of the precursor to product ion at m/z 405.6 → 220.9 for lesinurad and m/z 285.1 → 192.8 for IS. The assay was well validated for selectivity, accuracy, precision, recovery, linearity, matrix effects, and stability. The verified method was applied to obtain the pharmacokinetic parameters and concentration–time profiles for lesinurad after oral/intravenous administration in rats. The study might provide an important reference and a necessary complement for the qualitative and quantitative evaluation of lesinurad.Electronic supplementary materialThe online version of this article (10.1186/s13065-017-0353-6) contains supplementary material, which is available to authorized users.

Ultra-performance hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry for simultaneous determination of allopurinol, oxypurinol and lesinurad in rat plasma: Application to pharmacokinetic study in rats

“…Several methods have been reported in literature for simultaneous determination of ALP and OXP in human plasma [ 20 – 24 ]. Recently, Zhou XY et al, described the assay for the determination of LES in rat plasma by UPLCMS/MS method [ 25 ]. Since LES is therapeutically used in combination only with XOIs, and after approval of FDC of ALP and LES, a validated assay is required for simultaneous determination of ALP, OXP and LES in plasma.…”

A novel quality by design approach for development and validation of a green reversed‐phase HPLC method with fluorescence detection for the simultaneous determination of lesinurad, febuxostat, and diflunisal: Application to human plasma

“…From the literature survey, few methods were reported for LES analysis either alone or in combination with other drugs. The reported methods involve LC-MS/MS [10,11], HPLC-UV detection [12,13], CZE [14], and spectrofluorimetry [15,16]. Concerning FEB, a number of HPLC methods had been reported using photo diode array [8,17], fluorescence [18,19], and mass detection [20][21][22].…”

UHPLC–MS/MS‐based method for quantification of verinurad in rat plasma and its application in a bioavailability study

“…The AUC last was measured in 5016 ± 530 h*ng/mL, and the AUC INF_obs was in 5187 ± 607 h*ng/mL. The absolute bioavailability was 78.1% reflected verinurad is absorbed more quickly in vivo than the first‐generation inhibitor of URAT1 lesinurad (Zhou et al, 2017).…”