Liquid chromatography-tandem mass spectrometric assay for the light sensitive survivin suppressant sepantronium bromide (YM155) in mouse plasma

• A simple validated bioanalytical LC-MS/MS assay for YM155 has been reported.
• The assay has successfully been validated in the 0.5–100 ng/ml range for mouse plasma.
• The light sensitive drug is sufficiently stable under all conditions relevant for the assay.
• Drug levels in mice with neuroblastoma xenografts have been reported.

A quantitative bioanalytical liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay for sepantronium bromide (YM155), an inhibitor of survivin, was developed and validated. Under reduced light exposure, plasma samples were pre-treated using protein precipitation with acetonitrile containing AT7519 as internal standard. After dilution with water, the extract was directly injected into the reversed-phase liquid chromatographic system. The eluate was transferred into the electrospray interface with positive ionization and compounds detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer.The assay was validated in a 0.5–100 ng/ml calibration range with r2 = 0.9981 ± 0.0007 using double logarithmic calibration (n = 5). Within day precisions (n = 6) were 3.6–8.8% and between day (3 days; n = 18) precisions 6.5–11.1%. Accuracies were between 92 and 111% for the whole calibration range. The light sensitive drug sepantronium was sufficiently stable under all relevant analytical conditions. Finally, the assay was successfully used to determine plasma drug levels in mice after administration of sepantronium bromide by continuous infusion from subcutaneously implanted osmotic pumps.

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