CN106018573B - 一种tas-102中盐酸替比拉西的纯度检测方法 - Google Patents
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Abstract
本发明公开了一种TAS‑102中盐酸替比拉西的纯度检测方法，采用十八烷基硅烷键和硅胶为填充剂的色谱柱（250mmX4.6mm，5um），以等比例的改性缓冲溶液、有机相为流动相，以等度洗脱的方式在常温条件下检测替比拉西的纯度，实现对盐酸替比拉西质量的准确控制。
Description
技术领域
本发明涉及一种高效液相色谱法，特别是采用一种TAS-102中盐酸替比拉西的高效液相色谱纯度检测方法。
背景技术
TAS-102为新型组合抗代谢药物，由三氟胸苷与盐酸替比拉西组成。盐酸替比拉西可以抑制和三氟胸苷分解相关的胸腺嘧啶磷酸化酶，从而维持三氟胸苷的血液浓度，减少三氟胸苷的降解。盐酸替比拉西的分子式：C5H5ClN2O2,化学名为，其结构式如下：
为了有效延长盐酸替比拉西的出峰时间并与溶剂峰及杂质峰完全分离，改善出峰峰型，进而准确控制盐酸替比拉西的质量，目前很难查询到盐酸替比拉西的纯度检测相关高效液相色谱方法。
发明内容
本发明的目的在于克服盐酸替比拉西极性大，从而导致在高效液相色谱中出峰早，不能很好地和溶剂峰及杂质峰分离，且峰型也不佳的困难，提供一种采用等度洗脱实现盐酸替比拉西出峰时间较晚与溶剂峰及杂质峰能完全分离，且峰型佳的方法，实现对盐酸替比拉西质量的准确控制。
本发明涉及的一种TAS-102中盐酸替比拉西高效液色谱纯度检测方法，包括以下步骤：
(1)取盐酸替比拉西样品适量，用有机溶剂溶解盐酸替比拉西样品，配制成每1ml含盐酸替比拉西0.8mg～1.2mg的样品溶液；
(2)设置液相色谱仪的流动相，即A泵为有机相，B泵为改性缓冲盐，设置液相色谱仪的等度洗脱程序为A：B＝75:25，洗脱时间：15min。
(3)设置液相色谱仪的流动相流速0.8～1.2ml/min、检测波长220nm±3nm，以及设置液相色谱仪色谱柱的柱温箱25～35℃；
(4)取步骤(1)的样品溶液10ul注入经步骤(2)(3)设置的液相色谱仪，完成替比拉西的纯度检测；
进一步的所述步骤(1)的有机溶剂为甲醇或乙醇。
所述的液相色谱仪所采用十八烷基键合硅胶为填充剂的色谱柱，色谱柱的规格为长度250mm、内径4.6mm、粒度5um。
所述步骤(2)的有机相为乙腈或甲醇。
所述步骤(2)的改性缓冲溶液为20mmol的磷酸水或磷酸盐。
所述步骤(2)的有机相和缓冲溶液的比例为75:25，洗脱时间为15min。
本发明采用十八烷基键合硅胶为填充剂的色谱柱，能有效检测盐酸替比拉西的纯度；选择甲醇为溶剂，确保样品能完全溶解；选择进样体积10ul，柱温为30℃，提高了色谱峰的对称性；选择流速1.0ml/min，能延迟出峰时间；选择A泵为甲醇，B泵为缓冲溶液20mmol磷酸氢二铵+10mmol庚烷磺酸钠+0.1％三氟乙酸，调节PH值至3.5，采用等度洗脱实现了盐酸替比拉西和溶剂峰及杂质峰的完全分离，实现了盐酸替比拉西的纯度检测，对实现盐酸替比拉西在TAS-102合成和制剂生产过程中的质量控制方面具有现实意义。
附图说明
下面结合附图对本发明技术方案作进一步说明：
图1为本发明实施例1的高效液相色谱图；
图2为本发明实施例2的高效液相色谱图；
图3为本发明实施例3的高效液相色谱图。
具体实施方式
下面结合附图来说明本发明。
实施例1
采用安捷伦1260型号高效液相色谱仪、Ecosil品牌十八烷基键合硅胶为填充剂的色谱柱，色谱柱的规格为长度250mm、内径4.6mm、粒度5um。
一种TAS-102中盐酸替比拉西的高效液相色谱纯度检测方法，包括以下步骤：
(1)取盐酸替比拉西8mg，溶于10ml容量瓶中，加入甲醇溶解并定容至刻度，摇匀，即为供试液；
(2)设置液相色谱仪的流动相，即A泵为有机相，B泵为缓冲溶液，以及设置液相色谱仪的比例为：A:B＝25：75，洗脱时间为15min；
(3)设置液相色谱仪的流速为0.8ml/min，检测波长217nm，以及设置液相色谱仪色谱柱的柱温箱25℃；
(4)取步骤(1)的供试品溶液10ul注入经(2)(3)设置的液相色谱仪中，完成盐酸替比拉西的纯度检测，记录色谱图，结果见附图1。
图1中盐酸替比拉西的保留时间为8.831min，3.837min分离度为10.95,4.744分离度为6.50,6.447分离度为7.98,8.831分离度为8.30，完全符合《2015版中国药典》分离度不小于1.5的规定，峰纯度为0.99，对称因子为0.62，均符合规定。
实施例2
采用安捷伦1260型号高效液相色谱仪、Ecosil品牌十八烷基键合硅胶为填充剂的色谱柱，色谱柱的规格为长度250mm、内径4.6mm、粒度5um。
一种TAS-102中盐酸替比拉西的高效液相色谱纯度检测方法，包括以下步骤：
(1)取盐酸替比拉西10mg，溶于10ml容量瓶中，加入甲醇溶解并定容至刻度，摇匀，即为供试液；
(2)设置液相色谱仪的流动相，即A泵为有机相，B泵为缓冲溶液，以及设置液相色谱仪的比例为：A:B＝25：75，洗脱时间为15min；
(3)设置液相色谱仪的流速为1ml/min，检测波长220nm，以及设置液相色谱仪色谱柱的柱温箱30℃；
(4)取步骤(1)的供试品溶液10ul注入经(2)(3)设置的液相色谱仪中，完成盐酸替比拉西的纯度检测，记录色谱图，结果见附图2。
附图2中盐酸替比拉西的保留时间为7.065min，3.207min分离度为9.21,4.007min分离度为6.66,5.277min分离度为7.28,7.065min分离度为7.82，完全符合《2015版中国药典》分离度不小于1.5的规定，峰纯度为0.99，对称因子为0.63，均符合相关规定。
实施例3
采用安捷伦1260型号高效液相色谱仪、Ecosil品牌十八烷基键合硅胶为填充剂的色谱柱，色谱柱的规格为长度250mm、内径4.6mm、粒度5um。
一种TAS-102中盐酸替比拉西的高效液相色谱纯度检测方法，包括以下步骤：
(1)取盐酸替比拉西12mg，溶于10ml容量瓶中，加入甲醇溶解并定容至 刻度，摇匀，即为供试液：
(2)设置液相色谱仪的流动相，即A泵为有机相，B泵为缓冲溶液，以及设置液相色谱仪的比例为：A:B＝25：75，洗脱时间为15min
(3)设置液相色谱仪的流速为1ml/min，检测波长223nm，以及设置液相色谱仪色谱柱的柱温箱35℃
(4)取步骤(1)的供试品溶液10ul注入经(2)(3)设置的液相色谱仪中，完成盐酸替比拉西的纯度检测，记录色谱图，结果见附图3
图3中盐酸替比拉西的保留时间为5.850min，2.740min分离度为7.86,4.023min分离度为9.45,4.446min分离度为2.25,5.850min分离度为6.92，完全符合《2015版中国药典》分离度不小于1.5的规定，峰纯度为0.99，对称因子为0.66，均符合相关规定。
上述实施例只为说明本发明的技术构思及特点，其目的在于让熟悉此项技术的人士能够了解本发明的内容并加以实施，并不能以此限制本发明的保护范围，凡根据本发明精神实质所作的等效变化或修饰，都应涵盖在本发明的保护范围内。
Claims (2)
1.一种TAS-102中盐酸替比拉西的高效液相色谱纯度检测方法，包括以下步骤：
(1)取盐酸替比拉西样品适量，用有机溶剂溶解盐酸替比拉西样品，配制成每1ml含盐酸替比拉西0.8mg～1.2mg的样品溶液：
(2)设置液相色谱仪的色谱柱，色谱柱的填充剂为十八烷基键合硅胶，色谱柱的规格为长度250mm、内径4.6mm、粒度5um；设置液相色谱仪的流动相，流动相为甲醇：20mmol/L磷酸二氢铵+10mmol/L庚烷磺酸钠+0.1％三氟乙酸调节pH值至3.5的缓冲盐溶液＝75:25，洗脱时间：15min；
(3)设置液相色谱仪的流动相流速0.8～1.2ml/min、检测波长220nm±3nm，以及设置液相色谱仪色谱柱的柱温箱25-35℃；
(4)取步骤(1)的样品溶液10ul注入经步骤(2)、(3)设置的液相色谱仪，完成盐酸替比拉西的纯度检测。
2.根据权利要求1所述的一种TAS-102中盐酸替比拉西高效液色谱纯度检测方法，其特征是：所述步骤(1)的有机溶剂为甲醇或乙醇。
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| 6-[(2-Iminopyrrolidinyl)methyl]-5-[I-125]iodouracil as a potential thymidine phosphorylase-targeted radiopharmaceutical: synthesis and preliminary biological evaluation;Mukai, Takahiro; Taketomi, Masato; Tashiro, Masaaki;《JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS》;20090126;第52卷(第5期);146-150 * |
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