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 C(18) (50 mm x 2.1 mm i.d., 3.5 microm) 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.
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA.
Ming
M
Zhao
Ping
P
He
Linping
L
Xu
Manuel
M
Hidalgo
Dan
D
Laheru
Michelle A
MA
Rudek
D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood* / Q000302:isolation & purification; D002853:Chromatography, Liquid / Q000379:methods*; D005204:Farnesol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000302:isolation & purification; D006801:Humans; D012459:Salicylates / Q000008:administration & dosage / Q000097:blood* / Q000302:isolation & purification; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000970:Antineoplastic Agents; D012459:Salicylates; C093323:farnesylthiosalicylic acid; D005204:Farnesol