The characterisation of synthetic and natural-product pharmaceuticals by electrospray ionisation-mass spectrometry (ESI-MS) and liquid chromatography (LC)-ESI-MS

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

“…Results compiled in Table 2 ) that can be generated from any of compounds 4. DHQ has also been previously found as the major product of MS 2 fragmentation of nicotine [34].…”

“…Loss of a small amine involving formation of a new cyclic species has been also described for MS 2 -fragmentation of nicotine, but in such case the pathway for methylamine release with concomitant formation of 7,8-dihydroquinoline is considerably simpler than the one illustrated in Scheme 4A [34]. Notwithstanding, the loss of 17 or 16 a.m.u.…”

“…Other examples where MS 2 fragmentation leads to cleavage of a C-N bond with amine release are mostly found for tertiary amines, as these have C-N bond dissociation energies (BDE) lower than those of their secondary amine counterparts [31]. For instance, the ESI-MS behavior of therapeutically relevant tertiary amines has been described by Smyth and co-workers to involve fragmentation to smaller amines [34,47], as nicely reviewed in [31]. Amine release is also common in MS 2 fragmentations of oligopeptides, though through different pathways, as for instance the y 7 fragmentation of the bioactive octapeptide Angiotensin II, corresponding to loss of the N-terminal Asp residue as 3-aminodihydrofuran-2,5-dione.…”

“…ESI-MS n studies of antimalarial compounds as bisthiazolium or quinolines can be found on reports by Nicolas et al [38] or Smyth et al and O'Donnell et al [34,39], respectively. However, ESI-MS studies contributing to the development of antimalarials are scarce.…”

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

“…Overall, this work embodies an original and valuable contribution towards a deeper insight into the molecular properties of novel antimalarials, which can be viewed as representative of both the O ver the past decade, electrospray ionization mass spectrometry (ESI-MS) has been used for the most diverse analytical purposes. This technique has provided deeper insight into the structural properties and stability of numerous compounds, from natural products [1][2][3] to synthetic drugs [4][5][6][7][8], peptides [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23], and heterocycles [24][25][26][27][28], among many others. 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.…”