title: Investigation into omacetaxine solution stability for in vitro study.
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.
authors.affiliation: Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, Davidson Building, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: Lamin
authors.initials: L
authors.lastname: Marenah
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Allan
authors.forename: Joanne C
authors.initials: JC
authors.lastname: Mountford
authors.forename: Tessa L
authors.initials: TL
authors.lastname: Holyoake
authors.forename: Heather G
authors.initials: HG
authors.lastname: Jørgensen
authors.forename: Moira A
authors.initials: MA
authors.lastname: Elliott
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006248:Harringtonines / Q000737:chemistry*; D000077863:Homoharringtonine; D006863:Hydrogen-Ion Concentration; D012996:Solutions / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
chemical_list: D006248:Harringtonines; D012996:Solutions; D000077863:Homoharringtonine