高效液相色谱法测定创新药物艾托莫德原料药中的有关物质

目的：建立高效液相色谱法测定抗银屑病新药艾托莫德（SYL927）原料药中有关物质的含量。方法：采用HC-C₈色谱柱（4.6 mm×250 mm，5 μm），以乙腈-0.2%醋酸钠缓冲液为流动相进行梯度洗脱，流速1.0 mL·min^-1，柱温40℃，检测波长283 nm，进样量20 μL。对SYL927与合成工艺中的6种中间体和3种副产物的分离分析方法进行了验证。结果：SYL927与9种有关物质可完全分离，分离度大于1.5。所有的有关物质在线性范围内线性关系良好，r均大于0.999 9；检测下限均在0.5~2 ng范围，定量下限均在1~4 ng范围；平均回收率（n=7）在100.2%~101.4%，RSD均≤2.2%。3批样品的总杂质含量≤1.0%。结论：该方法适用于艾托莫德原料药有关物质的控制和稳定性考察。

Objective:To establish an HPLC method for the determination of related substances in a new anti-psoriasis drug aituomode(SYL927)bulk drug. Methods:Separation was performed on an HC-C₈ chromatography column(4.6 mm×250 mm,5 μm),and the detection wavelength was 283 nm. The mobile phase was acetonitrile-0.2% sodium acetate buffer solution,with gradient elution at a flow rate of 1.0 mL·min^-1. The column temperature was 40℃ and the injection volume was 20 μL. The method was validated for the determination of the related substances in aituomode bulk drugs,including 6 kinds of intermediates and 3 kinds of by-products. Results:SYL927 and all the related substances were well separated,with the resolution greater than 1.5. All of the analytes was good linear relationships(r>0.999 9)in the linear range. The detection limits were 0.5-2 ng,and the quantification limits were 1-4 ng,respectively. The average recoveries(n=7)were between 100.2% and 101.4%,with the RSD ≤ 2.2%. The total content of related substances in each of the three batches of aituomode samples was less than 1.0%. Conclusion:The method was suitable for the quality control and stability test of aituomode bulk drug.

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