title: Nature of the main contaminant in the anti malaria drug primaquine diphosphate: a qualitative isomer analysis.
abstract: The main contaminant of primaquine (CAS 90-34-6) has been tentatively identified, by using two liquid chromatography (LC) methods and liquid chromatography-mass spectrometry (LC-MS), as the positional isomer quinocide (CAS 525-61-1). The first LC system was equipped with a chiral Chirex (S)-VAL and (R)-NEA column and the second system was equipped with an Adsorbosphere Nucleotide-Nucleoside 7 micro column. Comparison of the main contaminant of primaquine with an authentic quinocide standard by using co-chromatography in both LC systems and LC-MS (mass fragmentation) supported the hypothesis. The toxicity of quinocide batch 17172, primaquine batch 16039, and the drug primaquine diphosphate batch 20107 used in pharmaceutical industry, and the effect of the substances on respiratory and electron transport chain were compared in the eucaryotic unicellular fresh water green alga Chlamydomonas reinhardtii as a model system. These studies suggest that minor amount of other related substances can contribute more to the toxicity of the drug primaquine diphosphate than the positional isomer quinocide.
authors.affiliation: Department of Biochemistry, University of Oslo, P.O. Box 1041, Blindern, Oslo 0316, Norway. ilia.brondz@biokjemi.uio.no
authors.forename: Ilia
authors.initials: I
authors.lastname: Brondz
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mantzilas
authors.forename: Uwe
authors.initials: U
authors.lastname: Klein
authors.forename: Dag
authors.initials: D
authors.lastname: Ekeberg
authors.forename: Erlend
authors.initials: E
authors.lastname: Hvattum
authors.forename: Marina N
authors.initials: MN
authors.lastname: Lebedeva
authors.forename: Felix S
authors.initials: FS
authors.lastname: Mikhailitsyn
authors.forename: Gasan D
authors.initials: GD
authors.lastname: Souleimanov
authors.forename: Johan
authors.initials: J
authors.lastname: Røe
mesh_terms: D000634:Aminoquinolines / Q000032:analysis / Q000633:toxicity; D000818:Animals; D000962:Antimalarials / Q000032:analysis* / Q000633:toxicity; D001681:Biological Assay; D016825:Chlamydomonas reinhardtii / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D002734:Chlorophyll / Q000032:analysis / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004340:Drug Contamination; D004566:Electrodes; D004579:Electron Transport / Q000187:drug effects; D008027:Light; D013058:Mass Spectrometry; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D010788:Photosynthesis / Q000187:drug effects; D011319:Primaquine / Q000032:analysis* / Q000633:toxicity; D012015:Reference Standards; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D002734:Chlorophyll; C010775:quinocide; D011319:Primaquine; D010100:Oxygen