替格瑞洛中异构体杂质的控制  

Determination of isomers in ticagrelor

作　　者：霍立茹 薛晓婷 赵卿 张慧 

机构地区：[1]南京济群医药科技有限公司,南京210000 [2]中国药科大学,南京211198

出　　处：《药物分析杂志》2017年第11期2006-2012,共7页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立手性拆分的正相高效液相色谱方法检测替格瑞洛中的异构体。方法:采用硅胶表面涂布直链淀粉-三(3,5-二甲苯基氨基甲酸酯)为填充剂的手性色谱柱(250 mm×4.6 mm,5μm,Chiralpak AD-H色谱柱);以正己烷-无水乙醇-异丙醇-三氟乙酸(90∶5∶5∶0.1)为流动相;流速:1.0 m L·min^(-1);柱温:40℃;检测波长:245 nm。结果:替格瑞洛与各异构体在该色谱条件下专属性及分离度良好;方法进样精密度良好;色谱条件发生细微变化时对主成分与异构体的分离无显著影响,方法的耐用性良好;替格瑞洛、非对映异构体Ⅰ、非对映异构体Ⅱ、对映异构体的定量限分别为0.21、0.49、0.26、0.38μg·m L^(-1);检测限分别为0.053、0.024、0.07、0.01μg·m L^(-1),均能达到检测灵敏度要求;重复性良好;在相应的线性范围内,线性关系均良好,相关系数均在0.999以上;加样回收率分别为99.1%、100.5%、101.4%,RSD分别为1.5%、1.6%、1.3%,均符合标准,说明该方法准确度良好。替格瑞洛溶液于室温、室内散光条件下放置8 h,均未检出异构体,且主成分无明显变化,说明溶液稳定性良好。结论:建立的替格瑞洛异构的体检查方法专属性强、检测灵敏度高、准确度高,可用于替格瑞洛异构体的检测。Objective： To establish a chiral normal phase high performance liquid chromatography （ HPLC ） method for the detection of ticagrelor and its isomers. Methods： The chromatographic separation was on Chiralpak AD-H column （ 250 mm × 4.6 mm, 5 μm ）. The mobile phase consisted of hexane-ethanol- isopropanol -trifluoroacetic acid （ 90 ： 5：5：0.1 ） at the flow rate of 1.0 mL · min-1. The column temperature was 40℃ and the detection wavelength was 245 nm. Results： Both of ticagrelor and its isomers could be separated completely and had good specificity in the chromatographic conditions. The resolution had no great changes when chromatographic conditions changed slightly. It indicated the good tolerance. The limits of quantitation of ticagrelor, diastereoisomer Ⅰ , diastereoisomer Ⅱ , enantiomer were 0.21,0.49, 0.26, 0.38 μg· mL-1, respectively; and the detection limits were 0.053,0.024, 0.07, 0.01 μg· mL-1, respectively. It indicated that the method had good linear relationship between the linear ranges with the correlation coefficient more than 0.999. The recoveries of the isomers were 99.1%, 100.5%, 101.4%, respectively and RSDs were 1.5%, 1.6% and 1.3%, respectively. It indicated that the method had great accuracy. The isomers were not detected when ticagrelor was placed at room temperature and indoor astigmatism for 8 hours without significant change of the peak area of ticagrelor simultaneously. It proved the solution of ticagrelor was stable. Conclusion： The method is specific, sensitive and accurate and can be used to determine ticagrelor and its isomers.

关 键 词：抗血小板药物 替格瑞洛 异构体 高效液相色谱 手性拆分 正相色谱 

分 类 号：R917[医药卫生—药物分析学]