Nature of the main contaminant in the anti malaria drug primaquine diphosphate: a qualitative isomer analysis

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 μ 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.