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目的建立了手性固定相高效液相色谱法拆分富马酸替诺福韦二吡呋酯对映异构体的方法。方法采用高效液相色谱法,色谱柱为Chiralcel OD-H(500mm×4.6mm,5μm,Daicel),以环己烷-无水乙醇(95:5)为流动相(含0.2%的二乙胺),检测温度为20℃。该方法经过线性、重复性、检测限、定量限和方法抗干扰性的验证。结果富马酸替诺福韦二吡呋酯及异构体在此条件下能够很好地分离,分离度为1.78。异构体的检测限和定量限分别为0.005μg和0.015μg。S异构体在原料药中的回收率为98.68%~109.21%,样品溶液和流动相在72h内稳定。结论该方法能成功的用于富马酸替诺福韦二吡呋酯及异构体的分离,并且能够重现性好的准确定量原料药中的S异构体。
OBJECTIVE To establish a method for the separation of tenofovir disoproxil fumarate enantiomers by high performance liquid chromatography with chiral stationary phase. Methods Chromatography was performed on a Chiralcel OD-H (500 mm × 4.6 mm, 5 μm, Daicel) column using cyclohexane-absolute ethanol (95: 5) as mobile phase containing 0.2% ), The detection temperature is 20 ℃. The method is validated by linearity, repeatability, limit of detection, limit of quantitation and method anti-interference. Results Tenofovir disoproxil fumarate and isomers were well separated under this condition with a resolution of 1.78. The limit of detection and the limit of quantification for the isomers were 0.005 μg and 0.015 μg, respectively. The recoveries of S isomers in APIs ranged from 98.68% to 109.21%. The sample solution and mobile phase were stable within 72 hours. Conclusion This method can be successfully applied to the separation of tenofovir disoproxil fumarate and its isomers, and can accurately quantify the S isomers in drug substances with reproducibility.