4-Methylamino antipyrine determination in human plasma by high-performance liquid chromatography tandem mass spectrometry.

In the present study, a simple and rapid method for metamizole metabolite 4-methylamino antipyrine (MAA) determination in human plasma was developed, validated and successfully applied to a clinical trial. Chromatographic separation was achieved in HILIC mode on a YMC-Pack SIL column (100 × 2.0 mm; S-5 µm, 30 nm), with a mobile phase consisting of acetonitrile, water and formic acid. Protein precipitation of a small plasma volume using acetonitrile was selected for sample preparation. The multiple reaction monitoring transitions in the positive ionization mode were m/z 218.2 → 56.2 for MAA and m/z 221.2 → 56.2 for MAA-d3 (IS, internal standard). Concentration levels of MAA calibration standards were in the range of 0.100-20 µg/ml. Metamizole conversion into MAA in both water and organic media was investigated, and the level of the conversion in commercially available injection solutions was estimated.

HPLC-MS/MS method for troventol determination in human plasma and its application to biological samples.

For the first time, an HPLC-MS/MS method for the determination pmol/l levels of troventol (TRV) and clenbuterol as an internal standard (IS) in human plasma was developed, validated and tested on biological samples. The method included solid phase extraction by Waters Oasis WCX cartridges and chromatographic separation on a YMC-Pack SIL (100mm×2.1mm, 5µm, 12nm) analytical column with acetonitrile-water-formic acid (50:50:0.1, v/v/v) as the mobile phase; the selected ion transitions were m/z 332.2→138.2 and m/z 277.0→203.1 for TRV and IS, respectively, in positive ionization mode. The calibration curve for TRV showed good linearity in the concentration range of 35-500pg/ml. The method was applied to real samples taken from healthy subjects after inhalation of an aerosol containing 640µg of TRV.

The role of attentional bias in mediating human drug-seeking behaviour.

RATIONALE: The attentional bias for drug cues is believed to be a causal cognitive process mediating human drug seeking and relapse. OBJECTIVES, METHODS AND RESULTS: To test this claim, we trained smokers on a tobacco conditioning procedure in which the conditioned stimulus (or S+) acquired parallel control of an attentional bias (measured with an eye tracker), tobacco expectancy and instrumental tobacco-seeking behaviour. Although this correlation between measures may be regarded as consistent with the claim that the attentional bias for the S+ mediated tobacco seeking, when a secondary task was added in the test phase, the attentional bias for the S+ was abolished, yet the control of tobacco expectancy and tobacco seeking remained intact. CONCLUSIONS: This dissociation suggests that the attentional bias for drug cues is not necessary for the control that drug cues exert over drug-seeking behaviour. The question raised by these data is what function does the attentional bias serve if it does not mediate drug seeking?