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目的建立他达拉非原料药中对映异构体和非对映异构体的定量分析方法。方法采用CHIRALPAK-IC(250 mm×4.6 mm,5μm)色谱柱,流动相为乙腈-水(40∶60),流速为1.0 m L·min~(-1),检测波长为222 nm,柱温为30℃,进样量20μL。加校正因子的自身稀释对照法计算异构体含量,其中异构体A、异构体B和异构体C的校正因子分别为1.22,1.07和1.25。结果他达拉非及异构体A、异构体B和异构体C峰分离良好,分离度>1.5,异构体A、异构体B和异构体C分别在25.3~379.5,50.6~379.5,50.4~378.0 ng·m L~(-1)内线性关系良好(r为0.997 3~0.998 7),加样回收率分别为107.5%,96.9%,98.5%(n=9),进样精密度RSD≤2%,重复性RSD分别为1.44%,1.64%和4.89%。检测限分别为12.7,25.3,25.2 ng·m L~(-1)。3批样品中异构体A最高含量为0.018%,异构体B及异构体C均未超过检测限(<0.010%)。结论该方法简单,准确,重复性好,可用于他达拉非原料药中对映异构体和非对映异构体的测定。
Objective To establish a method for the quantitative analysis of enantiomers and diastereomers in tadalafil APIs. Methods The chromatographic column was CHIRALPAK-IC (250 mm × 4.6 mm, 5 μm). The mobile phase was acetonitrile-water (40:60) at a flow rate of 1.0 mL · L -1 and the detection wavelength was 222 nm. 30 ℃, injection volume 20μL. The isoforms content was calculated using the self-dilution control plus calibration factors, with the correction factors for isomer A, isomer B and isomer C being 1.22, 1.07 and 1.25, respectively. Results Tadalafil and its isomer A, isomer B and isomer C peaks were well separated with resolution> 1.5. Isomer A, isomer B and isomer C were 25.3 ~ 379.5 and 50.6 respectively ~ 379.5,50.4 ~ 378.0 ng · m L ~ (-1) (r = 0.997 3 ~ 0.998 7). The average recoveries were 107.5%, 96.9% and 98.5%, respectively The precision of RSD was less than or equal to 2%, and the repeatability RSD was 1.44%, 1.64% and 4.89% respectively. The detection limits were 12.7, 25.3 and 25.2 ng · m L -1, respectively. The highest content of isomer A in three batches of samples was 0.018%, and none of isomer B and isomer C exceeded the detection limit (<0.010%). Conclusion The method is simple, accurate and reproducible. It can be used for the determination of enantiomers and diastereomers in tadalafil APIs.