Quantification of Antimalarial Bisthiazolium Compounds and Their Neutral Bioprecursors in Plasma by Liquid Chromatography-Electrospray Mass Spectrometry

Abstract

؉ at m/z 568 and m/z 596, respectively. The sample clean-up procedure involved solid-phase extraction. HPLC separation was performed on a reversed-phase column, using a water-acetonitrile gradient, with both solvents containing TFA. Stability under various conditions was also investigated. Results: The peak-area ratios (drugs/internal standard) were linked to concentrations (6.4 -1282 g/L for T3;

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

“…Synthesis of compounds PQAAPro mimetics (5). The synthetic route to Structures 5 is depicted in Scheme 1a-e.…”

“…Ion 10a (Scheme 2) was selected for MS n fragmentation studies on PQAAPro mimetics (5). Loss of 85 Da was the main, and often the only, event registered on MS 3 spectra of these compounds, so that the MS Table S3).…”

“…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.…”

“…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.…”

Hypoxanthine guanine phosphoribosyltransferase activity is related to 6-thioguanine nucleotide concentrations and thiopurine-induced leukopenia in the treatment of inflammatory bowel disease

“…In IBD patients, this may occurred as early as the initial weeks of instituting the therapy. 29,30 TPMT testing is now recommended for patients with clinical or laboratory evidence of severe bone marrow toxicity, particularly myelosuppression. 31 But the distribution of TPMT mutant alleles differs significantly among ethnic populations.…”