A sensitive and selective liquid chromatography/tandem mass spectrometry method for determination of MLN8237 in human plasma

J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Sep 1;878(25):2369-73. doi: 10.1016/j.jchromb.2010.06.037. Epub 2010 Jul 3.


We describe a selective and a highly sensitive high-performance liquid chromatography-electron spray ionization-collision induced dissociation-tandem mass spectrometry (HPLC-ESI-CID-MS/MS) assay for the Aurora A kinase inhibitor MLN8237 in human plasma. The intra-day precision based on the standard deviation of replicates of quality control samples ranged from 0.2 to 4% and with accuracy ranging from 96 to 102%. The inter-day precision ranged from 0.5 to 7% and the accuracy ranged from 93 to 105%. Stability studies showed that MLN8237 was stable both during the expected conditions for sample preparation and storage. The lower limit of quantification for MLN8237 was 5 ng/mL. The analytical method showed excellent sensitivity, precision, and accuracy. This method is robust and is being successfully employed in a Children's Oncology Group Phase 1 Consortium study of MLN8237 in children with cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinases
  • Azepines / blood*
  • Chromatography, Liquid / methods*
  • Drug Stability
  • Humans
  • Least-Squares Analysis
  • Protein Kinase Inhibitors / blood
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Pyrimidines / blood*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry / methods*


  • Azepines
  • MLN 8237
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases