关闭
 
读者在线:用户名 密码
首页 期刊简介 投稿须知 期刊目录 专家风采 编委会 特邀顾问 联系我们 移动出版
  1. 1
  2. 2
  3. 3
  4. 4
  5. 5



刊物信息

期刊名称:药物分析杂志
主管单位:中国科学技术协会
主办单位:中国药学会
承办:中国食品药品检定研究院
主编:金少鸿
地址:北京天坛西里2号
邮政编码:100050
电话:010-67012819,67058427
电子邮箱:ywfx@nicpbp.org.cn
国际标准刊号:ISSN 0254-1793
国内统一刊号:CN 11-2224/R
邮发代号:2-237
 

访问统计
您是第  2 7 7 6 3 2 6 位浏览者
您当前的位置:首页 >> 正文

替格瑞洛中异构体杂质的控制

Determination of isomers in ticagrelor

作者(英文):
分类号:R917
出版年·卷·期(页码):2017,37 (11):2006-2012
DOI: 10.16155/j.0254-1793.2017.01.01
-----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,5 μm,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 mL·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、0.38 μg·mL-1;检测限分别为0.053、0.024、0.07、0.01 μg·mL-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。

-----英文摘要:---------------------------------------------------------------------------------------

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.

-----参考文献:---------------------------------------------------------------------------------------
[1] 缪世峰,蔺宇,张海波,等.新型抗凝血药替格瑞洛的合成[J].海峡药学,2015,27(4):249 MIAO SF,LIN Y,ZHANG HB,et al.Synthesis of novel anticoagulant ticagrelor[J].Strait Pharm J,2015,27(4):249
[2] ZHANG H,LIU J,ZHANG LY,et al.Synthesis and biological evaluation of ticagrelor derivatives as novel antiplatelet agents[J].Bioorg Med Chem Lett,2012(22):3598
[3] 李慕鹏,熊艳,陈小平.抗血小板药物替格瑞洛药代药效动力学及遗传药理学研究进展[J].中国临床药理学与治疗学,2014,19(2):214 LI MP,XIONG Y,CHEN XP.Research progress in pharmacodynamics and pharmacogenetics of antiplatelet Ticagrelor[J].Chin J Clin Pharmacol Ther,2014,19(2):214
[4] 王仙,朱慧,胡燕,等.抗血小板聚集新药-替格瑞洛[J].医院药学杂志,2013,33(11):900 WANG X,ZHU H,HU Y,et al.The novel antiplatelet drug-Ticagrelor[J].Chin Hosp Pharm J,2013,33(11):900
[5] 马文涛,颜红兵.新型的口服抗血小板药物替格瑞洛[J].中华老年心脑血管病杂2012,14(11):1217 MA WT,TAN HB.Novel oral antiplatelet drug-Ticagrelor[J].Chin J Geriatr Heart Brain Vessel Dis,2012,14(11):1217
[6] 张金彦,吉绍长.药物的手性拆分[J].化学通报,2013,76(8):725 ZHANG JY,JI SC.Chiral separation of medicines[J].Chem Bull,2013,76(8):725
[7] 杨庆云,王志鹏,邓愉凤,等.正相高效液相色谱法拆分普拉克索对映异构[J].药物分析杂志,2014,34(11):2005 YANG QY,WANG ZP,DENG YF,et al.Chiral separation of pramipexole enantiomers by normal phase high performance liquid chromatography[J].Chin J Pharm Anal,2014,34(11):2005
[8] 苏镜娱,郑义森.对映异构体光学拆分法的进展[J].药学学报,1985,20(9):710 SU JY,ZHENG YS.Enantiomer progress of optical resolution method[J].Acta Pharm Sin, 1985,20(9):710
[9] 黄蓓,杨立荣,吴坚平.手性拆分技术的工业应用[J].化工进展,2002,21(6):375 HUANG B,YANG LR,WU JP.Chiral resolution techniques in industrial practice[J].Chem Ind Eng Prog,2002,21(6):375
[10] 翁文,姚碧霞,陈秀琴,等.液相色谱手性拆分机理的热力学方法研究[J].化学进展,2006,18(7/8):1056 WENG W,YAO BX,CHEN XQ,et al.Thermodynamic studies on mechanism of chiral resolution by liquid chromatography[J].Prog Chem,2006,18(7/8):1056
[11] 朱晓峰,林炳承.毛细管电泳的手性拆分[J].色谱,1999,17(2):153 ZHU XF,LIN RC. Chiral resolution of capillary electrophoresis[J].Chin J Chromgr,1999,17(2):153
[12] 李根荣,李志良.手性药物拆分技术研究进展[J].中国新药杂志,2005,14(8):969 LI GR,LI ZL.Advances in the chiral drug resolutions[J].Chin J New Drugs,2005,14(8):969
[13] 王林.对映异构体的薄层色谱直接拆分法[J].国外医学药学分册,1992,19(4):205 WANG L.Enantiomorphism isomers TLC separation method directly[J].Foreign Med Sci Sec Pharm,1992,19(4):205
[14] 于海云,宋俊梅,陈志从.利用手性固定相高效液相色谱法对焦谷氨酸对映异构体的分离[J].中国现代药物应用,2011, 5(21):83 YU HY,SONG JM,CHEN ZC.The separation of glutamic acid enantiomorphism isomers by chiral stationary phase high performance liquid chromatography[J].Chin J Mod Drug Appl,2011, 5(21):83
[15] 赵静,邹卫,赵华,等.手性固定相正相高效液相色谱法拆分普萘洛尔对映体[J].光谱实验室,2011,28(1):7 ZHAO J,ZOU W,ZHAO H,et al.The separation of propranolol enantiomers by Chiral stationary phase normal high performance liquid chromatography[J].Chin J Spectr Lab,2011, 28(1):7
[16] 韩小茜,魏燕,刘艳华,等.氟环唑外消旋体在纤维素-三(3, 5-二甲基苯基氨基甲酸酯)手性固定相上的高效液相色谱法拆分[J].色谱,2008,9:631 HAN XQ,WEI Y,LIU YH,et al.Chiral separation of racemic epoxiconazoleon cellulose tris (3, 5-dimethyl phenyl carbamate) chiral stationary phase using high performance liquid chromatography[J].Chin J Chromgr,2008,9:631
[17] 丁黎.药物色谱分析[M].北京:人民卫生出版社,2008:162 DING L.Chromatographic Analysis of Drugs[M].Beijing:People's Medical Publishing House,2008:162

欢迎阅读《药物分析杂志》!您是该文第 240位读者!

药物分析杂志 © 2009
地址:北京天坛西里2号
邮政编码:100050; 技术支持:010-60213898

电子邮件:ywfx@nicpbp.org.cn