Determination of salirasib ( S- trans, trans-farnesylthiosalicylic acid) in human plasma using liquid chromatography–tandem mass spectrometry

Abstract

A liquid chromatography/tandem mass spectrometric (LC/MS/MS) assay was developed for the quantitative determination of salirasib ( S- trans, trans-farnesylthiosalicylic acid, FTS) in human plasma. Sample pretreatment involved liquid–liquid extraction with methyl t-butyl ether of 0.5-mL aliquots of lithium heparin plasma spiked with the internal standard, S- trans, trans-5-fluoro-farnesylthiosalicylic acid (5-F-FTS). Separation was achieved on Waters X-Terra™ C 18 (50 mm × 2.1 mm i.d., 3.5 μm) at room temperature using isocratic elution with acetonitrile/10 mM ammonium acetate buffer mobile phase (80:20, v/v) containing 0.1% formic acid at a flow rate of 0.20 mL/min. Detection was performed using electrospray MS/MS by monitoring the ion transitions from m/z 357.2 → 153.0 (salirasib) and m/z 375.1 → 138.8 (5-F-FTS). Calibration curves were linear in the concentration range of 1–1000 ng/mL. A 5000 ng/mL sample that was diluted 1:10 (v/v) with plasma was accurately quantitated. The values for both within day and between day precision and accuracy were well within the generally accepted criteria for analytical method (<8.0%). This assay was subsequently used for the determination of salirasib concentrations in plasma of cancer patients after oral administration of salirasib at a dose of 400 mg.