Chromatographic methods for the separation of bicompatible iron chelators from their synthetic precursors and iron chelates
Chromatographic methods for the separation of bicompatible iron chelators from their synthetic precursors and iron chelates
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DOI：
10.1002/jssc.200401878
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发表时间：
2004-12-01
影响因子：
3.1
通讯作者：
Vávrová, K
中科院分区：
文献类型：
--
作者：
Kovaríková, P;Mokry, M;Vávrová, K
建立了三种新型生物相容铁络合剂吡哆醛-异烟酰肼(PIH)、水杨醛-异烟酰肼(SIH)和吡哆醛-2-氯苯甲酰肼(OMICRON-108)的分离方法。色谱柱为5微米Nucleosil 120-5 C-18色谱柱。为了在合成前体存在的情况下评价所有的螯合剂，在流动相中加入浓度为2 mM的EDTA。磷酸盐缓冲液(0.01M磷酸二氢钠，5 mM 1-庚烷磺酸钠；pH 3.0)-甲醇(55：45，v/v)分离效果最佳。以0.01M磷酸盐缓冲液(pH 6.0)-甲醇(60：40，v/v)为流动相分离SiH及其合成前体。OMICRON-108采用0.01M磷酸盐缓冲液(pH 7.0)、甲醇和乙腈(60：20：20，v/v/v)的混合物进行分析。对这些流动相进行了轻微的修饰，将每个螯合剂从其铁络合物中分离出来。此外，还建立了一种快速分离所有化合物的RP-TLC方法。本文所述的层析方法可用于评价这些候选药物的纯度和稳定性。
Chromatographic methods have been developed for the separation of the three novel biocompatible iron chelators pyridoxal isonicotinoyl hydrazone (PIH), salicylaldehyde isonicotinoyl hydrazone (SIH), and pyridoxal 2-chlorobenzoyl hydrazone (omicron-108) from their synthetic precursors and iron chelates. The chromatographic analyses were achieved using analytical columns packed with 5 mum Nucleosil 120-5 C-18. For the evaluation of all chelators in the presence of the synthetic precursors, EDTA was added to the mobile phase at a concentration of 2 mM. The best separation of PIH and its synthetic precursors was achieved using a mixture of phosphate buffer (0.01 M NaH2PO4, 5 mM 1-heptanesulfonic acid sodium salt; pH 3.0) and methanol (55:45, v/v). For separation of SIH and its synthetic precursors, the mobile phase was composed of 0.01 M phosphate buffer (pH 6.0) and methanol (60:40, v/v). omicron-108 was analyzed employing a mixture of 0.01 M phosphate buffer (pH 7.0), methanol, and acetonitrile (60:20:20, v/v/v). These mobile phases were slightly modified to separate each chelator from its iron chelate. Furthermore, a RP-TLC method has also been developed for fast separation of all compounds. The chromatographic methods described herein could be applied in the evaluation of purity and stability of these drug candidates.