Determination of PF‐04620110, a novel inhibitor of diacylglycerol acyltransferase‐1, in rat plasma using liquid chromatography–tandem mass spectrometry and its application in pharmacokinetic studies

In this study, we developed a method for the determination of PF‐04620110 (2‐{(1r,4r)‐4‐[4‐(4‐amino‐5‐oxo‐7,8‐dihydropyrimido[5,4‐f][1,4]oxazepin‐6(5H)‐yl)phenyl]cyclohexyl}acetic acid), a novel diacylglycerol acyltransferase 1 (DGAT‐1) inhibitor, in rat plasma and validated it using liquid chromatography–tandem mass spectrometry (LC‐MS/MS). Rat plasma samples were processed following a protein precipitation method by using acetonitrile and were then injected into an LC‐MS/MS system for quantification. PF‐04620110 and imipramine (internal standard) were separated using a Hypersil Gold C₁₈ column, with a mixture of acetonitrile and 10 mm ammonium formate (90:10, v/v) as the mobile phase. The ion transitions monitored in positive‐ion mode [M + H]⁺ of multiple‐reaction monitoring were m/z 397.0 → 260.2 for PF‐04620110 and m/z 280.8 → 86.0 for imipramine. The detector response was specific and linear for PF‐04620110 at concentrations within the range 0.05–50 µg/mL and the signal‐to‐noise ratios for the samples were ≥10. The intra‐ and inter‐day precision and accuracy of the method matched the acceptance criteria for assay validation. PF‐04620110 was stable under various processing and/or handling conditions. PF‐04620110 concentrations in the rat plasma samples could be measured up to 24 h after intravenous or oral administration of PF‐04620110, suggesting that the assay is useful for pharmacokinetic studies in rats. Copyright © 2013 John Wiley & Sons, Ltd.     

A novel cyclization/oxidation strategy for a two-step synthesis of (Z)-aurone

An efficient and facile two-step strategy for the synthesis of (Z)-aurone from arylacetylenes and salicyladehydes, via silver(I) nitrate mediated cyclization/oxidation in the presence of potassium carbonate has been developed. The key feature of our method was delicate cascade reaction, to provide the corresponding (Z)-aurone in high yield and good regio- and stereo selectivity.     

Applicability of in situ detectors for radiological assessment of strontium-90 in rivers and lakes

Journal of Radioanalytical and Nuclear Chemistry - An in situ detector for radiological assessments of strontium-90 (90Sr) in river and lake water is developed, based on a CaF2(Eu) scintillator,...     

Structure and transmittance behavior of sol–gel silica nanoparticles synthesized using pH-stable alkanolamines

Journal of Sol-Gel Science and Technology - Although sol–gel silica nanoparticles are widely used in academic and industrial applications, only a few studies have focused on amine catalysts...     

Anion Recognition by Urea Derivatives of Anthraquinone: Dihydrogen Phosphate Ion Selective Neutral Receptors

Three urea derivatives of anthraquinone were synthesized and they showed a high selectivity for dihydrogen phosphate ions.