Liquid chromatography–electrospray tandem mass spectrometric assay suitable for quantitation of YM155, a novel small‐molecule survivin suppressant, in dog plasma

This paper describes a sensitive and selective liquid chromatography with tandem mass spectrometry (LC–MS/MS) method for determination of the novel survivin suppressant YM155, 1‐(2‐methoxyethyl)‐2‐methyl‐4,9‐dioxo‐3‐(pyrazin‐2‐ylmethyl)‐4,9‐dihydro‐1 H ‐naphtho[2,3‐ d ]imidazolium, which is developed for the treatment of solid tumors. This method uses a liquid–liquid extraction from 0.25 mL of dog plasma. LC separation was carried out on a Genesis Silica column (50 mm × 3.0 mm i.d.) at a flow‐rate of 0.5 mL/min. Compounds were eluted using a mobile phase of 5 m m ammonium acetate and 0.1% formic acid in water–0.1% formic acid in acetonitrile, 17:83 (v/v). MS/MS detection was carried out with an MDS‐Sciex API3000 triple quadrupole mass spectrometer in positive electrospray ionization mode. The standard curve was linear from 0.05 to 50 ng/mL ( r ≥ 0.9968). The lower limit of quantitation was 0.05 ng/mL. Good intra‐ and inter‐day assay precision (within 7.4% RSD) and accuracy (within ±12.3%) were obtained. The extraction recovery was 66.2%. The method was successfully applied to preclinical pharmacokinetic studies in dogs. Copyright © 2008 John Wiley & Sons, Ltd.