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

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™ C18 (50mm×2.1mm i.d., 3.5μm) at room temperature using isocratic elution with acetonitrile/10mM ammonium acetate buffer mobile phase (80:20, v/v) containing 0.1% formic acid at a flow rate of 0.20mL/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 1–1000ng/mL. A 5000ng/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 400mg.