Liquid chromatography-tandem mass spectrometric assay for the JAK2 inhibitor CYT387 in plasma

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• 作者：Rolf W. Sparidans^a ; ^{R.W.Sparidans@uu.nl} ; Selvi Durmus^b ; Ning Xu^b ; Alfred H. Schinkel^b ; Jan H.M. Schellens^a ; ^c ; Jos H. Beijnen^a ; ^c ; ^d
• 关键词：HESI ; heated electrospray ionization ; JAK ; Janus kinase ; LLOQ ; lower limit of quantification ; SRM ; selected reaction monitoring ; QC ; quality control
• 刊名：Journal of Chromatography B ; Analytical Technologies in the Biomedical and Life Sciences
• 出版年：2012
• 期刊代码：124_15700232
• 类别：ch
• 出版时间：1 May, 2012
• 卷：895-896
• 期：Complete
• 页码：174-177
• 文件大小：269 K

摘要

A quantitative bioanalytical liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay for the JAK2 inhibitor CYT387 was developed and validated. Plasma samples were pre-treated using protein precipitation with acetonitrile containing cediranib as internal standard. The extract was directly injected into the chromatographic system after dilution with water. This system consisted of a sub-2 渭m particle, trifunctional bonded octadecyl silica column with a gradient using 0.005%(v/v) of formic acid in a mixture of water and methanol. The eluate was transferred into the electrospray interface with positive ionization and the analyte was detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer. The assay was validated in a 0.25-1000 ng/ml calibration range. Within day precisions were 3.0-13.5%, between day precisions 5.7%and 14.5%. Accuracies were between 96%and 113%for the whole calibration range. The drug was stable under all relevant analytical conditions. Finally, the assay was successfully used to assess drug levels in mice.