title: Liquid chromatography-tandem mass spectrometric assay for the light sensitive survivin suppressant sepantronium bromide (YM155) in mouse plasma.
abstract: 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 0.5-100ng/ml calibration range with r(2)=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.
authors: Amsterdam Medical Center, University of Amsterdam, Department of Oncogenomics, Meibergdreef 15, PO Box 22700, 1105 AZ Amsterdam, The Netherlands.
authors: M Emmy M
authors: ME
authors: Dolman
authors: Amsterdam Medical Center, University of Amsterdam, Department of Oncogenomics, Meibergdreef 15, PO Box 22700, 1105 AZ Amsterdam, The Netherlands.
authors: Ilona J M
authors: IJ
authors: den Hartog
authors: Amsterdam Medical Center, University of Amsterdam, Department of Oncogenomics, Meibergdreef 15, PO Box 22700, 1105 AZ Amsterdam, The Netherlands.
authors: Jan J
authors: JJ
authors: Molenaar
authors: Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands; The Netherlands Cancer Institute, Department of Clinical Pharmacology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors: Jan H M
authors: JH
authors: Schellens
authors: Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands; The Netherlands Cancer Institute, Department of Clinical Pharmacology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Slotervaart Hospital, Department of Pharmacy & Pharmacology, Louwesweg 6, 1066 EC Amsterdam, The Netherlands.
authors: Jos H
authors: JH
authors: Beijnen
authors: Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands. Electronic address: R.W.Sparidans@uu.nl.
authors: Rolf W
authors: RW
authors: Sparidans
mesh_terms: D000818:Animals; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D007093:Imidazoles / Q000737:chemistry*; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors*; D008027:Light; D051379:Mice; D009285:Naphthoquinones / Q000737:chemistry*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors*; D015203:Reproducibility of Results; D000077022:Survivin; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C117749:Birc5 protein, mouse; D007093:Imidazoles; D051034:Inhibitor of Apoptosis Proteins; D009285:Naphthoquinones; D012097:Repressor Proteins; D000077022:Survivin; C523798:sepantronium
keywords: LC-MS/MS; Plasma; Sepantronium bromide; Survivin suppressant