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. 2017 Nov 28;11(1):121.
doi: 10.1186/s13065-017-0353-6.

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

Xiao-Yang Zhou  1 , Ling-Jing Yuan  2 , Zhe Chen  2 , Peng-Fei Tang  2 , Xiang-Yu Li  2 , Guo-Xin Hu  2 , Jian-Ping Cai  3
Affiliations

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

Xiao-Yang Zhou et al. Chem Cent J. .

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.

Keywords: Lesinurad; Pharmacokinetics; Rat plasma; UHPLC–MS/MS.

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Figures

Fig. 1
Fig. 1
Chemical structures of a lesinurad and b diazepam (IS)
Fig. 2
Fig. 2
Representative UHPLC–MS/MS chromatograms of lesinurad and IS in rat plasma samples. a A blank plasma sample; b a blank plasma sample spiked with lesinurad and IS; c a rat plasma sample obtained 1 h after oral administration of lesinurad
Fig. 3
Fig. 3
Mean plasma concentration versus time curves after oral or intravenous administration of lesinurad in rats. a Oral administration (20 mg/kg); b intravenous administration (5 mg/kg)
See this image and copyright information in PMC

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