title: On-column epimerization of dihydroartemisinin: an effective analytical approach to overcome the shortcomings of the International Pharmacopoeia monograph.
abstract: We developed a cryo-HPLC/UV method for the simultaneous determination of artemisinin (1), alpha-dihydroartemisinin (2alpha), beta-dihydroartemisinin (2beta), and a ubiquitous thermal decomposition product of 2 (designated as diketoaldehyde, 3), starting from the International Pharmacopoeia monograph on dihydroartemisinin. The method takes for the first time the on-column epimerization process of 2 into consideration. Chromatographic separation was obtained under reversed-phase conditions on a Symmetry C18 column (3.5 microm particle size) with a mobile phase consisting of acetonitrile-water 60:40 (v/v), delivered at 0.60-1.00 ml/min flow-rates, with ultraviolet detection at low wavelength (lambda = 210 nm). Low temperatures (T = 0-10 degrees C) were selected on the grounds of a diastereoselective dynamic HPLC (DHPLC) study performed at different temperatures, aimed at identifying the best experimental conditions capable of minimizing the on-column interconversion process.
authors.affiliation: Analytical Development, R&D Department, sigma-tau S.p.A., Via Pontina km 30,400, 00040 Pomezia, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Cabri
authors.forename: Alessia
authors.initials: A
authors.lastname: Ciogli
authors.forename: Ilaria
authors.initials: I
authors.lastname: D'Acquarica
authors.forename: Michela
authors.initials: M
authors.lastname: Di Mattia
authors.forename: Bruno
authors.initials: B
authors.lastname: Galletti
authors.forename: Francesco
authors.initials: F
authors.lastname: Gasparrini
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Giorgi
authors.forename: Silvana
authors.initials: S
authors.lastname: Lalli
authors.forename: Marco
authors.initials: M
authors.lastname: Pierini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Simone
mesh_terms: D000962:Antimalarials / Q000032:analysis; D037621:Artemisinins / Q000032:analysis* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation* / Q000379:methods; D013696:Temperature
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C039060:artenimol