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Development and validation of a LC‐MS assay for the quantification of ikh12 a novel anti‐tumor candidate in rat plasma and tissues and its application in a pharmacokinetic study 下载免费PDF全文
Dorleta Otaegui Carme Masdeu Eneko Aldaba Yosu Vara Aizpea Zubia Eider San Sebastian Maria Alcalá Sergio Villafruela Fernando P. Cossío Alicia Rodriguez‐Gascón 《Biomedical chromatography : BMC》2015,29(8):1249-1258
IKH12 is a novel histone deacetylase 6 selective inhibitor. A rapid and sensitive liquid chromatography tandem mass spectrometry method was developed and validated for the quantification of IKH12 in rat plasma and tissue with kendine 91 as internal standard (IS). The samples were prepared by liquid–liquid extraction with tert‐butyl methyl ether. The chromatographic separation was accomplished by using a Zorbax Extend C18 4.6 × 150 mm, 5 µm column, with a mobile phase consisting of methanol and 0.1% formic acid (75:25 v/v). Multiple reaction monitoring, using electrospray ionization in positive ion mode, was employed to quantitatively detect IKH12 and IS. The monitored transitions were set at m/z 418 → 252 and 444 → 169 for IKH12 and kendine 91, respectively. The calibration curve was linear over the concentration range 2–1000 ng mL?1. The intra‐ and inter‐assay precision and accuracy of the quality controls and the limit of quantification were satisfactory in all cases (according to European Medicines Agency guidelines). Stability studies showed that plasma samples were stable in the chromatography rack for 24 h and at ?80 °C for 2 months and also after three freeze–thaw cycles. This method was successfully applied to a pharmacokinetic study of IKH12 in rat. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
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Arrieta A Otaegui D Zubia A Cossío FP Díaz-Ortiz A de la Hoz A Herrero MA Prieto P Foces-Foces C Pizarro JL Arriortua MI 《The Journal of organic chemistry》2007,72(12):4313-4322
The stereochemical outcomes observed in the thermal and microwave-assisted [3 + 2] cycloaddition between stabilized azomethine ylides and nitrostyrenes have been analyzed using experimental and computational approaches. It has been observed that, in the absence of solvent, three stereoisomers are formed, both under classical heating conditions and under microwave irradiation. This result contrasts with that observed in solution under classical thermal conditions. The 4-nitropyrrolidines obtained in this way can be aromatized under further microwave irradiation to yield mixtures of pyrroles and 4-nitropyrroles. It is found that ground state cycloadditions between imines and nitrostyrenes take place by three-step mechanisms. The first step involves enolization of the starting imine, and this is followed by a pseudopericyclic 10-electron [1.4]-hydrogen shift. Finally, the cycloaddition takes place by a relatively asynchronous aromatic six-electron supra-supra thermal mechanism. 相似文献
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