title: Nature of the main contaminant in the drug primaquine diphosphate: SFC and SFC-MS methods of analysis.
abstract: The drug primaquine diphosphate is used for causative treatment of malaria. Using HPLC-MS and GC-MS, this research group was previously able to show that the main contaminant of primaquine is the positional isomer quinocide [I. Brondz, D. Mantzilas, U. Klein, D. Ekeberg, E. Hvattum, M.N. Lebedeva, F.S. Mikhailitsyn, G.D. Soulimanov, J. Roe, J. Chromatogr. B: Anal. Technol. Biomed. Life Sci. 800 (2004) 211-223; I. Brondz, U. Klein, D. Ekeberg, D. Mantzilas, E. Hvattum, H. Schultz, F. S. Mikhailitsyn, Asian J. Chem. 17 (2005) 1678-1688]. Primaquine and quinocide are highly toxic substances which can have a number of side effects upon use in medical treatment. A standard for quinocide is not typically commercially available. In the present work, supercritical fluid chromatography-mass spectrometry (SFC-MS) with two different columns was used to achieve a shorter analysis time for the separation between the positional isomers quinocide and primaquine in primaquine diphosphate and to elucidate additional information about differences in their MS fragmentation. Unlike using HPLC-MS, it was possible to achieve the differential fragmentation of positional isomers at branching points using the SFC-MS technique. The desired short analysis time was achieved using SFC equipped with a Discovery HS F5 column and the differential fragmentation of positional isomers during SFC-MS provides information on the differences in the structure of these substances. Using a Chiralpak AD-H chiral column, it was possible to resolve the enantiomers in primaquine and separate quinocide from those enantiomers.
authors.affiliation: University of Life Sciences, Department of Chemistry, Biotechnology and Food Science, As, Norway. ilia.brondz@umb.no
authors.forename: Ilia
authors.initials: I
authors.lastname: Brondz
authors.forename: Dag
authors.initials: D
authors.lastname: Ekeberg
authors.forename: David S
authors.initials: DS
authors.lastname: Bell
authors.forename: Amy R
authors.initials: AR
authors.lastname: Annino
authors.forename: Jan Arild
authors.initials: JA
authors.lastname: Hustad
authors.forename: Robert
authors.initials: R
authors.lastname: Svendsen
authors.forename: Vaso
authors.initials: V
authors.lastname: Vlachos
authors.forename: Paul
authors.initials: P
authors.lastname: Oakley
authors.forename: G John
authors.initials: GJ
authors.lastname: Langley
authors.forename: Thite
authors.initials: T
authors.lastname: Mohini
authors.forename: Cazenave-Gassiot
authors.initials: CG
authors.lastname: Amaury
authors.forename: Felix
authors.initials: F
authors.lastname: Mikhalitsyn
mesh_terms: D000634:Aminoquinolines / Q000032:analysis; D000962:Antimalarials / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D025924:Chromatography, Supercritical Fluid; D013058:Mass Spectrometry; D011319:Primaquine / Q000032:analysis*; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; C010775:quinocide; D011319:Primaquine