Extending the use of “Inverted Chirality Columns Approach” for enantiomeric excess determination in absence of reference samples: Application to a water-soluble camptothecin derivative

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 CPT derivative, na...

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Bibliographic Details
Published in:Journal of Chromatography A 2010-02, Vol.1217 (7), p.1024-1032
Main Authors: Badaloni, Elena, Cabri, Walter, Ciogli, Alessia, D’Acquarica, Ilaria, Deias, Roberto, Gasparrini, Francesco, Giorgi, Fabrizio, Kotoni, Dorina, Villani, Claudio
Format: Article
Language:English
Subjects:
Anticancer drugs
Camptothecin (CPT) family
Chirality
Compatibility
Derivatives
Elution order reversal
Inverted Chirality Columns Approach (ICCA)
Namitecan (ST1968)
Optimization
Polarity
Recognition
Selectors
Terminals
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Summary: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 CPT 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 enantiomeric 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.
ISSN:0021-9673
DOI:10.1016/j.chroma.2009.10.035