title: A sensitive and selective liquid chromatography/tandem mass spectrometry method for determination of MLN8237 in human plasma.
abstract: 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.
authors.affiliation: Division of Clinical Pharmacology and Therapeutics, The Children's Hospital of Philadelphia, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Lipsitz
authors.forename: Ganesh
authors.initials: G
authors.lastname: Moorthy
authors.forename: Yael
authors.initials: Y
authors.lastname: Mosse
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fox
authors.forename: Peter C
authors.initials: PC
authors.lastname: Adamson
mesh_terms: D064127:Aurora Kinases; D001381:Azepines / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D016018:Least-Squares Analysis; D047428:Protein Kinase Inhibitors / Q000097:blood; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D001381:Azepines; C550258:MLN 8237; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases