Profiling primaquine metabolites in primary human hepatocytes using UHPLC‐QTOF‐MS with 13C stable isotope labeling

Therapeutic efficiency and hemolytic toxicity of primaquine (PQ), the only drug available for radical cure of relapsing vivax malaria are believed to be mediated by its metabolites. However, identification of these metabolites has remained a major challenge apparently due to low quantities and their reactive nature. Drug candidates labeled with stable isotopes afford convenient tools for tracking drug‐derived metabolites in complex matrices by liquid chromatography‐tandem mass spectrometry (LC‐MS‐MS) and filtering for masses with twin peaks attributable to the label. This study was undertaken to identify metabolites of PQ from an in vitro incubation of a 1:1 w/w mixture of ¹³C₆‐PQ/PQ with primary human hepatocytes. Acquity ultra‐performance LC (UHPLC) was integrated with QTOF‐MS to combine the efficiency of separation with high sensitivity, selectivity of detection and accurate mass determination. UHPLC retention time, twin mass peaks with difference of 6 (originating from ¹³C₆‐PQ/PQ), and MS‐MS fragmentation pattern were used for phenotyping. Besides carboxy‐PQ (cPQ), formed by oxidative deamination of PQ to an aldehyde and subsequent oxidation, several other metabolites were identified: including PQ alcohol, predictably generated by oxidative deamination of PQ to an aldehyde and subsequent reduction, its acetate and the alcohol's glucuronide conjugate. Trace amounts of quinone‐imine metabolites of PQ and cPQ were also detected which may be generated by hydroxylation of the PQ/cPQ quinoline ring at the 5‐position and subsequent oxidation. These findings shed additional light on the human hepatic metabolism of PQ, and the method can be applied for identification of reactive PQ metabolites generated in vivo in preclinical and clinical studies. Copyright © 2013 John Wiley & Sons, Ltd.     

Nucleon-antinucleon resonances near threshold: A possible explanation of the S(1930) meson

We suggest a dynamical mechanism (dominance of isoscalar meson exchange) which leads to an interpretation of the S(1930) meson in terms of a doublet of $\text{N}$N resonances with J^πC(I^G)=2^?+(0⁺, 1^?). The presence of a doublet implies constructive interference in the $\text{p}$p → $\text{p}$p elastic channel and destructive interference in the $\text{p}$p → $\text{n}$n channel, in agreement with recent experimental evidence. Possible spin and isospin assignments are suggested for other structures seen in $\text{N}$N cross sections near threshold.     

A high-throughput search for direct methanol fuel cell anode electrocatalysts of type PtxBiyPbz

We used a high-throughput method to screen for direct methanol fuel cell anode electrocatalysts in the Pt-Bi-Pb system. Previous studies showed that PtBi and PtPb (both NiAs structure type) were active electrocatalysts for the oxidation of formic acid, but only PtPb was active in oxidizing methanol. We synthesized thin films with continuous composition spreads of the three elements by magnetron sputtering at deposition temperatures from ambient to 510 °C. A fluorescence method was then used to identify compositions that were active toward methanol oxidation. Only films deposited between temperatures of 160 and 400 °C showed electrocatalytic activity. The areas that were active for methanol oxidation showed predominantly the NiAs structure type according to XRD, with optimal activity for compositions near PtBi_0.01Pb_0.53.