A simple and rapid UHPLC–MS/MS method for the quantitation of the dual aurora kinase A/B inhibitor SCH-1473759 in murine plasma

Marco A. Ferraz Nogueira Filho, Cody J. Peer, Jeffers Nguyen, Amy McCalla, Lee Helman, William D. Figg

Research output: Contribution to journalArticle

Abstract

The Aurora kinase family facilitates cell division through various processes and is overexpressed in a wide variety of human cancers, leading to aneuploidy. For that reason, these enzymes are currently targets of a rising class of anticancer drugs, with some molecules already in therapeutic use. In this study, a new UHPLC–MS/MS method was developed and validated to quantitate a new pan Aurora kinase inhibitor still in preclinical development, SCH-1473759. This bioanalytical method employed a liquid–liquid extraction from plasma using ethyl acetate before evaporation. Calibration range encompassed 0.5–2500 ng/mL. The inter- and intra-day accuracy and precision were assessed over five quality control levels; all within limits required by the FDA guidelines. Assay applicability was demonstrated in a first-in-animals study with oral administration, where the maximum plasma concentration (34 ng/mL) occurred at 1 h, the half-life (1 h) was consistent with a previous IV study, and oral bioavailability was poor (F = 0.002).

Original languageEnglish (US)
Pages (from-to)223-226
Number of pages4
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume132
DOIs
StatePublished - Jan 5 2017
Externally publishedYes

Fingerprint

Aurora Kinase B
Aurora Kinases
Aurora Kinase A
Liquid-Liquid Extraction
Aneuploidy
Quality Control
Cell Division
Calibration
Biological Availability
Oral Administration
Half-Life
Acetates
Enzymes
Neoplasms

Keywords

  • Aurora kinases
  • Mice
  • UHPLC–MS/MS pharmacokinetics

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

Cite this

A simple and rapid UHPLC–MS/MS method for the quantitation of the dual aurora kinase A/B inhibitor SCH-1473759 in murine plasma. / Ferraz Nogueira Filho, Marco A.; Peer, Cody J.; Nguyen, Jeffers; McCalla, Amy; Helman, Lee; Figg, William D.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 132, 05.01.2017, p. 223-226.

Research output: Contribution to journalArticle

Ferraz Nogueira Filho, Marco A.; Peer, Cody J.; Nguyen, Jeffers; McCalla, Amy; Helman, Lee; Figg, William D. / A simple and rapid UHPLC–MS/MS method for the quantitation of the dual aurora kinase A/B inhibitor SCH-1473759 in murine plasma.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 132, 05.01.2017, p. 223-226.

Research output: Contribution to journalArticle

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