Article ID Journal Published Year Pages File Type
1214544 Journal of Chromatography B 2011 7 Pages PDF
Abstract

A reversed-phased liquid chromatography with tandem mass spectrometry (LC–MS/MS) method was developed and validated for quantitation of the total and unbound RO4929097, a γ-secretase inhibitor targeting Notch signaling, in human plasma. Sample preparation involved a liquid–liquid extraction with ethyl acetate. Chromatographic separation was achieved on a Waters X-Terra™ MS C18 column with an isocratic mobile phase consisting of methanol/0.45% formic acid in water (60:40, v/v) running at a flow rate of 0.2 ml/min for 6 min. The lower limits of quantitation (LLOQs) were 5 ng/ml for the total RO4929097 in plasma and 0.5 ng/ml for the unbound drug in phosphate buffer solution (PBS). Calibration curves were linear over RO4929097 concentration range of 5–2000 ng/ml in plasma for the total drug and 0.5–200 ng/ml in PBS for the unbound drug. The intra-day and inter-day accuracy and precision were within the generally accepted criteria for bioanalytical method (<15%). The method has been successfully employed to characterize the total and unbound plasma pharmacokinetics of RO4929097 after its oral administration in cancer patients.

Related Topics
Physical Sciences and Engineering Chemistry Analytical Chemistry
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