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

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

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

@article{f9b86748830c4f7894740f03efaf679e,
title = "A simple and rapid UHPLC–MS/MS method for the quantitation of the dual aurora kinase A/B inhibitor SCH-1473759 in murine plasma",
keywords = "Aurora kinases, Mice, UHPLC–MS/MS pharmacokinetics",
author = "{Ferraz Nogueira Filho}, {Marco A.} and Peer, {Cody J.} and Jeffers Nguyen and Amy McCalla and Lee Helman and Figg, {William D.}",
year = "2017",
month = "1",
doi = "10.1016/j.jpba.2016.10.003",
volume = "132",
pages = "223--226",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
issn = "0731-7085",
publisher = "Elsevier",

}

TY - JOUR

T1 - A simple and rapid UHPLC–MS/MS method for the quantitation of the dual aurora kinase A/B inhibitor SCH-1473759 in murine plasma

AU - Ferraz Nogueira Filho,Marco A.

AU - Peer,Cody J.

AU - Nguyen,Jeffers

AU - McCalla,Amy

AU - Helman,Lee

AU - Figg,William D.

PY - 2017/1/5

Y1 - 2017/1/5

N2 - 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).

AB - 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).

KW - Aurora kinases

KW - Mice

KW - UHPLC–MS/MS pharmacokinetics

UR - http://www.scopus.com/inward/record.url?scp=84992490261&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84992490261&partnerID=8YFLogxK

U2 - 10.1016/j.jpba.2016.10.003

DO - 10.1016/j.jpba.2016.10.003

M3 - Article

VL - 132

SP - 223

EP - 226

JO - Journal of Pharmaceutical and Biomedical Analysis

T2 - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

ER -