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目的建立达比加群酯原料药中有关物质的测定方法。方法采用Agilent SB-C18色谱柱(250 mm×4.6 mm,5μm),以乙腈(A)-0.2%的醋酸铵(B,用冰醋酸调节p H值至4.4)为流动相进行梯度洗脱:0~18 min,90%→40%B;18~30 min,40%B。流速为1.0 m L·min~(-1),检测波长为340 nm。结果各杂质与主峰之间的分离度良好。5个已知杂质:杂质A浓度在0.117 0~1.872μg·m L~(-1)内与峰面积呈良好的线性关系,r为0.999 7;杂质B浓度在0.126 5~2.024μg·m L~(-1)内与峰面积呈良好的线性关系,r为0.999 5;杂质C浓度在0.113 0~1.808μg·m L~(-1)内与峰面积呈良好的线性关系,r为0.999 5;杂质D浓度在0.120 5~1.928μg·m L~(-1)内与峰面积呈良好的线性关系,r为0.999 9;杂质E浓度在0.123 0~1.968μg·m L~(-1)内与峰面积呈良好的线性关系,r为0.999 6;杂质A、杂质B、杂质C、杂质D和杂质E加样回收率的平均值分别为98.75%,98.91%,98.39%,99.0%和99.73%;RSD分别为0.91%,1.09%,1.22%,1.35%和1.18%。结论本方法简便、准确可靠,适用于达比加群酯中有关物质的控制。
Objective To establish a method for the determination of related substances in dabigatran etexilate. Methods The mobile phase was eluted with Agilent SB-C18 column (250 mm × 4.6 mm, 5 μm) using acetonitrile (A) -0.2% ammonium acetate (B, adjusted pH value to pH 4.4 with glacial acetic acid) 0-18 min, 90% → 40% B; 18-30 min, 40% B. The flow rate was 1.0 m L · min ~ (-1) and the detection wavelength was 340 nm. As a result, the degree of separation between each impurity and the main peak was good. Five known impurities: impurity A concentration in the range of 0.117 0 ~ 1.872μg · m L ~ (-1) and the peak area showed a good linear relationship, r is 0.999 7; impurity B concentration of 0.126 5 ~ 2.024μg · m L ~ (-1), and r is 0.999 5. The concentration of impurity C has a good linear relationship with the peak area in the range of 0.113 0 ~ 1.808 μg · m L ~ (-1), r is 0.999 5; the concentration of impurity D showed a good linear relationship with the peak area in the range of 0.120 5-1.928 μg · m L -1, r was 0.999 9; the concentration of impurity E was in the range of 0.123 0-1.968 μg · m L -1 ) Showed a good linear relationship with the peak area, r was 0.999 6; the average recoveries of impurity A, impurity B, impurity C, impurity D and impurity E were 98.75%, 98.91%, 98.39%, 99.0% And 99.73% respectively; RSD was 0.91%, 1.09%, 1.22%, 1.35% and 1.18% respectively. Conclusion This method is simple, accurate and reliable and is suitable for the control of related substances in dabigatran etexilate.