Zhou Xiao-Yang, Yuan Ling-Jing, Chen Zhe, Tang Peng-Fei, Li Xiang-Yu, Hu Guo-Xin, Cai Jian-Ping
The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, 100730, People's Republic of China.
Department of Pharmacology, School of Pharmacy, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
Chem Cent J. 2017 Nov 28;11(1):121. doi: 10.1186/s13065-017-0353-6.
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.
雷西纳德是一种尿酸阴离子交换转运体1的口服抑制剂，已获美国食品药品监督管理局批准，可与黄嘌呤氧化酶抑制剂联合用于治疗难治性痛风相关的高尿酸血症。在本研究中，首次建立并验证了一种灵敏且特异的超高效液相色谱-串联质谱法，用于测定大鼠血浆中的雷西纳德，并对其进行了详细描述。雷西纳德和地西泮（内标，IS）在Rapid Resolution HT C18柱（3.0×100 mm，1.8 µm）上进行色谱分离，以甲醇-水（70:30，v/v）为流动相，流速为0.3 mL/min。雷西纳德和内标通过乙酸乙酯液-液萃取从血浆中提取。质谱检测采用电喷雾电离源正离子模式。采用多反应监测对雷西纳德的m/z 405.6→220.9的前体离子到产物离子以及内标的m/z 285.1→192.8进行定量。该分析方法在选择性、准确性、精密度、回收率、线性、基质效应和稳定性方面均得到了良好验证。所验证的方法用于获取大鼠口服/静脉给药后雷西纳德的药代动力学参数和浓度-时间曲线。该研究可能为雷西纳德的定性和定量评估提供重要参考和必要补充。
