新型高选择性URAT1抑制剂HR011303的有关物质研究

目的： 研究用于痛风治疗的新型高选择性尿酸转运体1（URAT1）抑制剂HR011303原料药的有关物质。方法： 采用Agilent Eclipse Plus-XDB C₁₈（100 mm×4.6 mm，3.5 μm）色谱柱，以0.02 mol·L^-1磷酸二氢钠溶液（含0.1%三乙胺，磷酸调节pH 2.70）和乙腈为流动相，梯度洗脱，流速1.0 mL·min^-1，紫外检测波长230 nm。结果： HR011303与各有关物质的色谱峰能够完全分离，HR011303及杂质A、B、C的定量下限为0.39~1.00 ng，检测下限为0.12~0.30 ng；有关物质（杂质A、杂质B及杂质C）的主要来源为工艺和降解杂质。结论： 该方法可用于HR011303原料药的质量控制。有关物质的含量可以采用加校正因子的自身对照法计算。

Objective: To study the related substances of HR011303,a novel high selective urate transporter 1(URAT 1) inhibitor used for gout theament.Methods: The separation was carried out with Agilent Eclipse Plus-XDB C₁₈ column(100 mm×4.6 mm,3.5 μm)by gradient elution method,using a mixture of 0.02 mol·L^-1 sodium dihydrogen phosphate solution(containing 0.1% triethylamine,adjusted pH to 2.70 with phosphate acid)and acetonitrile as the mobile phase at a flow rate of 1.0 mL·min^-1,and the UV detection wavelength was set at 230 nm.Results: The peaks of HR011303 and related compounds can be separated completely.The lowest detection limits of HR011303 and impurities A,B,C was 0.12-0.30 ng,and the lowest quantification limits was 0.39-1.00 ng.The main sources of related substances(impurity A,impurity B,impurity C)are process and degradation impurities.Conclusion: The established method can be used for the quality control of HR011303,and impurities content can be calculated by using self-reference method with correction factors.

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