CN108037209B - 替格瑞洛手性中间体的液相色谱分析方法 - Google Patents
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- 229960002528 ticagrelor Drugs 0.000 title claims abstract description 37
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims abstract description 26
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000007864 aqueous solution Substances 0.000 claims abstract description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims abstract description 13
- 235000017557 sodium bicarbonate Nutrition 0.000 claims abstract description 13
- 238000002156 mixing Methods 0.000 claims abstract description 12
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims abstract description 10
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- 238000000034 method Methods 0.000 claims abstract description 10
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- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims 1
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Abstract
本发明提供了一种替格瑞洛手性中间体的液相色谱分析方法,其中所述手性中间体为2‑[[(3aR,4S,6R,6aS)‑6‑氨基四氢‑2,2‑二甲基‑4H‑环戊烯‑1,3‑二氧杂环戊烷‑4‑基]氧基]乙醇,包括以下步骤:分别精密量取替格瑞洛手性中间体溶液、碳酸氢钠水溶液、衍生试剂溶液,涡旋混匀,反应一定时间,再加入氯化氢水溶液,涡旋混匀,即得替格瑞洛手性中间体衍生物溶液;将所述替格瑞洛手性中间体衍生物溶液进行色谱分析。本发明的液相色谱分析方法能够准确灵敏地检测该手性中间体及其对映异构体的含量。
Description
技术领域
本发明涉及医药领域,具体涉及一种替格瑞洛手性中间体的液相色谱分析方法。
背景技术
2-[[(3aR,4S,6R,6aS)-6-氨基四氢-2,2-二甲基-4H-环戊烯-1,3-二氧杂环戊烷-4-基]氧基]乙醇是合成替格瑞洛(Ticagrelor)的重要手性中间体,其对映异构体2-[[(3aS,4R,6S,6aR)-6-氨基四氢-2,2-二甲基-4H-环戊烯-1,3-二氧杂环戊烷-4-基]氧基]乙醇通常存在于市售的替格瑞洛手性中间体产品中,两者的结构式分别如下:
上述替格瑞洛手性中间体及其对映异构体的紫外吸收均较弱,常规的带紫外检测器的高效液相色谱仪(HPLC)无法灵敏地检测该手性中间体及其对映异构体的含量,存在样品不易被检测的问题。因此,有必要研究能够准确灵敏地检测该手性中间体及其对映异构体的含量的分析方法,以便能够在后续的替格瑞洛合成工艺中有效控制替格瑞洛原料药的质量。
发明内容
为克服上述问题,本发明提供了一种灵敏、高效的替格瑞洛手性中间体的液相色谱分析方法,其中所述手性中间体为2-[[(3aR,4S,6R,6aS)-6-氨基四氢-2,2-二甲基-4H-环戊烯-1,3-二氧杂环戊烷-4-基]氧基]乙醇,所述方法包括以下步骤:
1)分别精密量取替格瑞洛手性中间体溶液、碳酸氢钠水溶液、衍生试剂溶液,涡旋混匀,反应一定时间,再加入氯化氢水溶液,涡旋混匀,即得替格瑞洛手性中间体衍生物溶液;
2)将替格瑞洛手性中间体衍生物溶液进行色谱分析。
在一个实施方案中,所述替格瑞洛手性中间体溶液、碳酸氢钠水溶液、衍生试剂溶液、氯化氢水溶液通过如下步骤来制备:
将替格瑞洛手性中间体溶解于稀释液中以制备所述替格瑞洛手性中间体溶液;
制备1mol/L碳酸氢钠水溶液;
将衍生试剂溶解于乙腈中以制备衍生试剂溶液;
制备1mol/L氯化氢水溶液。
在一个实施方案中,进行上述色谱分析的色谱仪器及条件为:
检测仪器:高效液相色谱仪,配备紫外检测器;
色谱条件:
色谱柱:Agilent ZORBAX XDB-C8 4.6×250mm,5um;流动相:流动相A:pH=3.0的磷酸盐缓冲溶液,流动相B:乙腈;检测波长:340nm;柱温:35℃;进样体积:20μL;样运行时间:55min;稀释液:pH=3.0的磷酸盐缓冲溶液-乙腈(70:30)。
在一个实施方案中,所述衍生试剂选自N-α-(5-氟-2,4-二硝基苯基)-L-丙氨酰胺(FDAA)其结构式如下:
进一步地,所述衍生试剂FDAA与替格瑞洛手性中间体及其对映异构体反应制备其对应的衍生物的原理如下:
另一方面,本发明还提供了衍生试剂用于替格瑞洛手性中间体的液相色谱分析的用途,其中所述手性中间体为2-[[(3aR,4S,6R,6aS)-6-氨基四氢-2,2-二甲基-4H-环戊烯-1,3-二氧杂环戊烷-4-基]氧基]乙醇。
在一个实施方案中,所述衍生试剂选自FDAA。
另一方面,本发明还提供了替格瑞洛手性中间体衍生物,其具有如下结构:
分别精密量取替格瑞洛手性中间体溶液、碳酸氢钠水溶液、衍生试剂溶液,涡旋混匀,反应一定时间,再加入氯化氢水溶液,涡旋混匀,得到所述化合物。
在一个实施方案中,所述替格瑞洛手性中间体溶液、碳酸氢钠水溶液、衍生试剂溶液、氯化氢水溶液通过如下步骤来制备:
将替格瑞洛手性中间体溶解于稀释液中以制备所述替格瑞洛手性中间体溶液;
制备1mol/L碳酸氢钠水溶液;
将衍生试剂溶解于乙腈中以制备衍生试剂溶液;
制备1mol/L氯化氢水溶液。
在一个实施方案中,所述衍生试剂选自FDAA。
本发明的有益效果在于:衍生试剂FDAA能将待测替格瑞洛手性中间体及其对映异构体在温和条件下在短时间内完全转化为其衍生物,衍生物紫外吸收较大,最大吸收波长达到340nm,而且所述衍生物在手性色谱中分离度较高,符合样品衍生化要求。
附图说明
图1为供试品衍生物溶液的HPLC谱图。
具体实施方案
检测仪器:高效液相色谱仪,配备紫外检测器
色谱条件:
色谱柱:Agilent ZORBAX XDB-C8 4.6×250mm,5um
流动相:流动相A:准确称取1.36g KH2PO4溶于1000mL超纯水中,用20%H3PO4溶液调pH至3.0;流动相B:乙腈
检测波长:340nm
流速:1.0mL/min
柱温:35℃
进样体积:20μL
运行时间:55min
流动相梯度:
溶液制备:
稀释液:流动相A-乙腈(70:30(v/v))。
供试品溶液:准确称取40mg替格瑞洛手性中间体样品(2-[[(3aR,4S,6R,6aS)-6-氨基四氢-2,2-二甲基-4H-环戊烯-1,3-二氧杂环戊烷-4-基]氧基]乙醇)于10mL容量瓶中,用超纯水溶解并稀释至刻度,摇匀。
5mg/mL衍生试剂溶液:准确称取50mg N-α-(5-氟-2,4-二硝基苯基)-L-丙氨酰胺于10mL容量瓶中,加乙腈溶解并稀释至刻度,摇匀。
1mol/L氯化氢水溶液:准确移取4.2mL浓盐酸于盛有少许超纯水的50mL容量瓶,并用超纯水稀释至刻度,摇匀。
1mol/L碳酸氢钠溶液:准确称取4.2g碳酸氢钠于50mL容量瓶中,用超纯水溶解并稀释至刻度,摇匀。
空白溶液:分别移取稀释液200μL、1mol/L碳酸氢钠溶液20μL、5mg/mL衍生试剂溶液500μL于反应瓶中,密封瓶盖,旋涡混匀,置于40℃水浴中反应2.5h(期间每隔30min振摇一次),取出,冷却至室温,再精密移取1mol/L氯化氢水溶液20μl于上述反应瓶中,旋涡混匀,即得。
供试品衍生物溶液:分别移取供试品溶液200μL、1mol/L碳酸氢钠溶液20μL、5mg/mL衍生试剂溶液500μL于反应瓶中,密封瓶盖,旋涡混匀,置于40℃水浴中反应2.5h(期间每隔30min振摇一次),取出,冷却至室温,再精密移取氯化氢水溶液20μL于上述反应瓶中,旋涡混匀,即得。
分别注入空白溶液和供试品衍生物溶液于高效液相色谱仪中,分别记录色谱图。供试品衍生物溶液的HPLC谱图见图1,其中对映异构体按照峰面积归一化计算。
Claims (4)
1.一种替格瑞洛手性中间体的液相色谱分析方法,其中所述手性中间体为2-[[(3aR,4S,6R,6aS)-6-氨基四氢-2,2-二甲基-4H-环戊烯-1,3-二氧杂环戊烷-4-基]氧基]乙醇,所述方法包括以下步骤:
1)分别精密量取替格瑞洛手性中间体溶液、碳酸氢钠水溶液、衍生试剂溶液,涡旋混匀,反应一定时间,再加入氯化氢水溶液,涡旋混匀,即得替格瑞洛手性中间体衍生物溶液;
2)将所述替格瑞洛手性中间体衍生物溶液进行色谱分析;
其中:
色谱柱:Agilent ZORBAX XDB-C8 4.6×250mm,5um
流动相:流动相A:准确称取1.36g KH2PO4溶于1000mL超纯水中,用20%H3PO4溶液调pH至3.0;流动相B:乙腈
流动相梯度:
其中,
所述衍生试剂为N-α-(5-氟-2,4-二硝基苯基)-L-丙氨酰胺,其结构式如下:
替格瑞洛手性中间体衍生物的结构如下所示:
2.根据权利要求1所述的方法,其特征在于,所述替格瑞洛手性中间体溶液、碳酸氢钠水溶液、衍生试剂溶液、氯化氢水溶液通过如下步骤来制备:
将所述替格瑞洛手性中间体溶解于稀释液中以制备所述替格瑞洛手性中间体溶液;
制备1mol/L碳酸氢钠水溶液;
将衍生试剂溶解于乙腈中以制备衍生试剂溶液;
制备1mol/L氯化氢水溶液。
3.根据权利要求2所述的方法,其特征在于,所述稀释液采用pH=3.0的磷酸盐缓冲溶液-乙腈,体积比为70:30。
4.根据权利要求1或2所述的方法,其特征在于,所述替格瑞洛手性中间体衍生物溶液的紫外检测波长为340nm。
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CN101788542B (zh) * | 2009-01-22 | 2012-07-04 | 上海臣邦医药科技有限公司 | 普瑞巴林及其手性异构体的分离检测方法 |
CN101968470B (zh) * | 2010-09-30 | 2013-11-20 | 湖北新生源生物工程股份有限公司 | 一种分离测定乙酰半胱氨酸对映异构体的方法 |
WO2012085665A2 (en) * | 2010-12-20 | 2012-06-28 | Actavis Group Patc Ehf | Novel processes for preparing triazolo[4,5-d]pyrimidine derivatives and intermediates thereof |
US20140206867A1 (en) * | 2011-06-15 | 2014-07-24 | Actavis Group Ptc Ehf | Process for Preparing Cyclopentylamine Derivatives and Intermediates Thereof |
CN105092721A (zh) * | 2014-05-21 | 2015-11-25 | 天津市汉康医药生物技术有限公司 | 一种控制替格瑞洛异构体的高效液相色谱检测分析方法 |
CN105319309A (zh) * | 2015-04-23 | 2016-02-10 | 北京紫萌同达科技有限公司 | 一种甘氨酰-l-谷氨酰胺手性异构体的分离检测方法 |
CN105301142A (zh) * | 2015-11-28 | 2016-02-03 | 重庆植恩药业有限公司 | 一种采用高效液相色谱检测替格瑞洛及其有关物质的方法 |
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