HPLC法测定甲苯磺酸索拉非尼中的有关物质

目的：建立HPLC法测定甲苯磺酸索拉非尼中的有关物质。方法：色谱柱为C₁₈柱（250 mm×4.6 mm，5 μm），流动相A为pH 2.4磷酸盐缓冲液（取磷酸二氢钾0.790 8 g，置1 000 mL水中，摇匀，用磷酸调节pH 2.4）-乙腈-乙醇（90∶6∶4），流动相B为pH 2.4磷酸盐缓冲液-乙腈-乙醇（20∶48∶32），进行梯度洗脱，流速为1.0 mL·min^-1，柱温为35℃，检测波长为235 nm。结果：索拉非尼与各已知杂质及强制破坏产生的降解产物均分离度良好，PAPE-氨基甲酸乙酯、CTF-苯胺、CTF-氨基甲酸乙酯、4-（4-氨基苯氧基）-N-甲基吡啶-2-甲酰胺质量浓度分别在0.567 0~5.670 2 μg·mL^-1（r=1.000）、0.569 1~5.691 0 μg·mL^-1（r=1.000）、0.573 5~5.734 8 μg·mL^-1（r=1.000）、0.556 4~5.564 4 μg·mL^-1（r=1.000）范围内与峰面积呈良好的线性关系，校正因子分别为3.2、1.1、1.6、2.1；定量下限分别为0.06、0.17、0.14、0.06 μg·mL^-1；回收率分别为99.5%、96.7%、99.3%、93.3%，RSD依次为0.69%、0.98%、0.65%、1.9%（n=9）。3批样品有关物质测定结果显示，已知杂质和未知杂质含量均低于0.10%。结论：该方法可用于甲苯磺酸索拉非尼有关物质的测定。

Objective: To establish an HPLC method for determination of related substances in sorafenib tosylate. Methods: C₁₈ column (250 mm×4.6 mm, 5 μm)was adopted. The mobile phase A was potassium dihydrogen phosphate buffer solution (dissolve 0.790 8 g of potassium dihydrogen phosphate in 1 000 mL of water, and adjust to pH 2.4 with phosphoric acid)-acetonitrile-ethanol (90:6:4);and the mobile phase B was potassium dihydrogen phosphate buffer solution-acetonitrile-ethanol (20:48:32)with gradient elution at the flow rate of 1.0 mL·min^-1. The column temperature was 35, and the detection wavelength was 235 nm. Results: Sorafenib tosylate was well separated from the specified impurities and the forced degradation products. There was a good linearity separately over the ranges 0.567 0-5.670 2 μg·mL^-1 (r=1.000)of PAPE-urethane, 0.569 1-5.691 0 μg·mL^-1 (r=1.000)of CTF-aniline, 0.573 5-5.734 8 μg·mL^-1 (r=1.000)of CTF-urethane, 0.556 4-5.564 4 μg·mL^-1 (r=1.000)of 4- (4-aminophenoxy)-N-methylpyridine-2-carboxamide. The correction factors were 3.2, 1.1, 1.6, 2.1, respectively. The limits of quantitation was 0.06 μg·mL^-1, 0.17 μg·mL^-1, 0.14 μg·mL^-1, 0.06 μg·mL^-1, respectively. The recovery rates were 99.5%, 96.7%, 99.3% and 93.3%, respectively. RSDs were 0.69%, 0.98%, 0.65% and 1.9% (n=9). The results of related substances in three batches of samples showed that the content of specified impurities and unknown impurities was less than 0.10%. Conclusion: The method is can be used for the determination of related substances in sorafenib tosylate.