CN102183589B - 一种多拉司琼异构体及其盐的含量的检测方法 - Google Patents
一种多拉司琼异构体及其盐的含量的检测方法 Download PDFInfo
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- CN102183589B CN102183589B CN 201010216160 CN201010216160A CN102183589B CN 102183589 B CN102183589 B CN 102183589B CN 201010216160 CN201010216160 CN 201010216160 CN 201010216160 A CN201010216160 A CN 201010216160A CN 102183589 B CN102183589 B CN 102183589B
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CN107703227B (zh) * | 2017-10-17 | 2020-11-13 | 成都新恒创药业有限公司 | 一种甲磺酸多拉司琼手性异构体的高效液相色谱检测方法 |
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Title |
---|
James S. McElvain, et al.Validation of a reversed-phase HPLC method for directly quantifying the enantiomers of MDL 74 156, the primary metabolite of dola mesylate, in human plasma.《Journal of Pharmaceutical and Biomedical Analysis》.1999,第15卷(第4期),513-521. * |
杨秀丽等.HPLC法测定甲磺酸多拉司琼的含量.《中国药房》.2007,第18卷(第22期),1731-1732. * |
潘红娟等.盐酸帕洛诺司琼注射液中异构体含量的NP-HPLC测定.《中国医药工业杂志》.2009,第40卷(第8期),610-612. * |
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