Nature of the main contaminant in the drug primaquine diphosphate: SFC and SFC–MS methods of analysis

Electrospray ionization-ion trap mass spectrometry study of PQAAPro and PQProAA mimetic derivatives of the antimalarial primaquine

“…Globally, the MS 2 fragmentation behavior of Structures 5 at NCE Ն 30% obeys to a general common pattern, with detachment of MAQ as the main fragmentation pathway. The elimination of MAQ (7) agrees with both our previous work [45] and the reported LC/ESI-MS characterization of PQ (1) and its major contaminant quinocide, carried out by Brondz et al [36]. Other relevant fragmentations were essentially based on concomitant and/or sequential loss of small molecules such as methane, water and alkylamines, involving opening of the imidazolidin-4-one ring while keeping the quinoline ring intact.…”

“…Notwithstanding, little has been done on the application of this technique to the study of relevant antimalarials such as primaquine (PQ, 1) or related structures. Analytical methods focused on PQ or its analogues have been so far applied to pharmacokinetics studies and metabolite scrutiny [29][30][31][32][33][34][35][36][37] or isomer characterization [38,39]. Examples of mass spectrometry techniques employed to the study/analysis of PQ and related compounds include fast atom bombardment mass spectral (FAB-MS) analysis of PQ oxidation products [32] and supercritical fluid chromatography-mass Address reprint requests to Dr. P.…”

“…Analytical methods focused on PQ or its analogues have been so far applied to pharmacokinetics studies and metabolite scrutiny [29][30][31][32][33][34][35][36][37] or isomer characterization [38,39]. Examples of mass spectrometry techniques employed to the study/analysis of PQ and related compounds include fast atom bombardment mass spectral (FAB-MS) analysis of PQ oxidation products [32] and supercritical fluid chromatography-mass spectrometry (SFC-MS) used to elucidate differences in the MS fragmentation patterns of PQ (free base), PQ diphosphate and its positional isomer quinocide and to achieve good resolution between these three compounds in short analysis times [36]. Apart from very few exceptions, such as the identification of the 8-aminoquinoline (8-AQ) NPC 1161 and its metabolites in biological samples [37], or studies on antimalarial compounds reported by Nicolas et al [5], Smyth et al and O'Donnell et al [I, 2], ESI-MS" techniques have seldom been employed to the characterization of antimalarial 8-AQ, and much less to PQ or its analogues.…”

Characterization of primaquine imidazolidin-4-ones with antimalarial activity by electrospray ionization-ion trap mass spectrometry

“…The diverse analytical methods focused on the antimalarial primaquine (PQ, 1, Scheme 1) or its analogues have been so far targeted at pharmacokinetics studies and metabolite analysis [1][2][3][4][5][6][7][8][9] or isomer separation/characterization [10,11]. The application of molecular modeling studies associated to voltammetric techniques showed to be an important way to understand the redox mechanism of electro-active drugs where aminoquinolines (AQs) such as PQ are included [7].…”

Analytical Methods in the Quality Control of Scientific Publications Part V: The Fraud of Pseudoscientists Based on False Measurements and Method Development

“…Several methods for determination of the toxic contaminant quinocide in raw ware primaquine and tablets have been published: [17] [18] by using GC-MS in 2004-2005, [19]- [21] by using HPLC and HPLC-MS in 2005, [22]- [24] by using SFC-MS in 2007-2009, and by using gas chromatography-mass spectrometry with supersonic molecular beams (SMB) in 2009 [25]. The biological consequences of primaquine contamination with quinocide were presented in 2011 [26].…”