期刊
JOURNAL OF CHROMATOGRAPHY A
卷 1217, 期 7, 页码 1024-1032出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.chroma.2009.10.035
关键词
Inverted Chirality Columns Approach (ICCA); Elution order reversal; Anticancer drugs; Camptothecin (CPT) family; Namitecan (ST1968)
资金
- FIRB [RBPR05NWWC-003]
The aim of the present study was to extend the use of the Inverted Chirality Columns Approach (ICCA) previously developed for the identification and quantitation of the trace enantiomer in highly enriched samples of the camptothecin (CPT) family of drugs to a novel water-soluble CVT derivative, namely namitecan (ST1968), currently undergoing phase I clinical trials as anticancer agent. Namitecan. identified from a series of hydrophilic 7-oxyiminomethyl derivatives, contains a free terminal amino group, which traditionally hampers the analysis under normal-phase HPLC conditions. Nevertheless, commercially available Pirkle-type chiral stationary phases (CSPs) available in both the enantionteric forms (i.e., having the same bound selector with opposite configuration) mainly operate under normal-phase HPLC conditions. For this reason, namitecan was pre-column N-protected with isocyanates A-D and their sulfur analogues E-H to reduce its polarity by converting the amino group into a fragment compatible with the chiral recognition mechanism (i.e., ureido and thioureido groups). Once the optimal columns system and derivatizing agents were selected, an original enantioselective HPLC-MS/MS technique was developed on the Whelk-O1 CsPs. (c) 2009 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据