Nature of the main contaminant in the drug primaquine diphosphate: SFC and SFC-MS methods of analysis.
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.
Brondz
Ilia
I
University of Life Sciences, Department of Chemistry, Biotechnology and Food Science, As, Norway. ilia.brondz@umb.no
Ekeberg
Dag
D
Bell
David S
DS
Annino
Amy R
AR
Hustad
Jan Arild
JA
Svendsen
Robert
R
Vlachos
Vaso
V
Oakley
Paul
P
Langley
G John
GJ
Mohini
Thite
T
Amaury
Cazenave-Gassiot
CG
Mikhalitsyn
Felix
F
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
D000634:Aminoquinolines; D000962:Antimalarials; C010775:quinocide; D011319:Primaquine