Investigation into omacetaxine solution stability for in vitro study

• Published in: Biomedical chromatography 2012-05, Vol.26 (5), p.545-547
• Main Authors: Marenah, Lamin, Allan, Elaine K., Mountford, Joanne C., Holyoake, Tessa L., Jørgensen, Heather G., Elliott, Moira A.
• Format: Article
• Language: English
• Subjects: Chromatography, High Pressure Liquid; chronic myeloid leukemia; Drug Stability; Harringtonines - chemistry; Hydrogen-Ion Concentration; omacetaxine; solution stability; Solutions - chemistry; Spectrophotometry, Ultraviolet; Temperature
• ISSN: 0269-3879; 1099-0801
• DOI: 10.1002/bmc.1686

ABSTRACT Omacetaxine is a natural product extract originating from Chinese medicine and finding therapeutic use as a potent myelosuppressive agent in leukemia. When planning in vitro cell biology experiments to assess omacetaxine activity against primary leukemic stem cells, it became apparent that the literature rarely describes the in vitro stability of the molecule, although accessible chromatographic methods have been published. Clearly whole organisms vs their component cells will differ in the way in which they handle xenobiotics, with the latter more dependent on physiochemical parameters such as pH and temperature in the absence of active metabolism or excretion. This could impact on the cells' experience of drug in culture. We therefore report here on examination of a modified, high‐performance liquid chromatography (HPLC) method with assessment of degradant production from a 72 h solution stability study, clearly demonstrating that omacetaxine is highly stable in representative cell culture conditions (37 °C, neutral pH) and persists for many days in marked contrast to its short‐half life in vivo. Copyright © 2011 John Wiley & Sons, Ltd.