建立了一种高效液相色谱(HPLC)法,用于检测甲苯磺酸依度沙班有关物质.该法采用SunFire C8(250 mm×4.6 mm,5 μm)色谱柱,以20 mmol/L磷酸氢二钾(pH 4.0)-乙腈(体积比为90∶10)为流动相A,20 mmol/L磷酸氢二钾(pH 4.0)-乙腈(体积比为30∶70)为流动相B,按梯度洗脱程序洗脱.该方法的检测波长为290 nm,流速为1.0 mL/min,柱温为30 ℃,进样量为10 μL.结果表明,甲苯磺酸依度沙班及各杂质均能有效分离;在相应的浓度范围内,各物质的线性关系良好;各杂质的回收率均在98.0%~102.0%,RSD(n=9)均小于2.0%;在色谱条件有微小变化时,各物质均能有效分离且杂质含量的差异在可接受范围内.经方法学验证,该方法专属性好、灵敏度高、准确度高、耐用性好,可用于甲苯磺酸依度沙班的质量控制.
A HPLC method was established to separate edoxaban tosilate hydrate and its related substances. SunFire C8(250 mm×4.6 mm, 5 μm)column was adopted in the analysis method and its temperature was kept at 30 ℃. The mobile phase A consisted of 20 mmol/L K2HPO4(pH 4.0)-acetonitrile(90∶10, V/V)and the mobile phase of B consisted of 20 mmol/L K2HPO4(pH 4.0)-acetonitrile(30∶70, V/V). A gradient elution at flow of 1.0 mL/min was used. The detection wavelength was 290 nm and the injection volume was 10 μL. The calibration curve of all substances were linear in appropriate concentration range, and the average recovery of all compounds were among 98.0%~102.0%, RSD(n=9)values were less than 2.0%. Each impurity was separated when the parameters had small changes and the assay variation of impurities was accepted. Methodology validation results proved that the method had good selectivity, high sensitivity, high accuracy and good robustness and it can be used for quality control of edoxaban tosilate hydrate.
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