Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Journal of pharmaceutical and biomedical analysis, 2017-01, Vol.132, p.223-226

Ort / Verlag

England: Elsevier B.V

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• [Display omitted] •We developed and validated a novel ultra HPLC–MS/MS assay for the quantification of SCH-1473759, a novel dual Aurora Kinase A/B inhibitor, in murine plasma.•This method is accurate, precise, and uses a simple liquid extraction procedure that recovers approximately 85% of drug from plasma.•SCH-1473759 demonstrated excellent freeze/thaw, and plasma stability.•This method was successfully applied to a first in vivo mouse pharmacokinetic study following oral gavage. 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 0.5–2500ng/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 (34ng/mL) occurred at 1h, the half-life (1h) was consistent with a previous IV study, and oral bioavailability was poor (F=0.002).