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Liquid chromatography-tandem mass spectrometry assay for therapeutic drug monitoring of the tyrosine kinase inhibitor, midostaurin, in plasma from patients with advanced systemic mastocytosis.

Abstract
We developed and validated quantitative bioanalytical liquid chromatography-tandem mass spectrometry assay for the protein kinase inhibitor, midostaurin. Plasma samples were pre-treated using a protein precipitation with methanol containing midostaurin-d5 as an internal standard. After centrifugation, 5μL of the supernatant was injected into the chromatographic system. The system consisted of a 3.5μm particle bonded octadecyl silica column, with gradient elution using a mixture of 0.1% (v/v) formic acid in acetonitrile and 10mM ammonium formate in water with 0.1% formic acid. The analyte was quantified using the selected reaction-monitoring mode of a triple quadrupole mass spectrometer equipped with a heated electrospray interface. The assay was validated in a 75-2500ng/mL calibration range. For quality control, within-day and between-day precisions were 1.2-2.8%, and 1.2-6.9%, respectively. The β-expectation tolerance limit (accuracy) met the limits of acceptance ±15% (±20% for the LLQ). The drug was sufficiently stable under all relevant analytical conditions. The assay has successfully been used to assess drug levels for therapeutic drug monitoring in patients presenting advanced systemic mastocytosis and treated with the promising midostaurin.
AuthorsPhilippe Bourget, Alexandre Amin, Marie-Olivia Chandesris, Fabrice Vidal, Christophe Merlette, Isabelle Hirsch, Laure Cabaret, Ana Carvalhosa, Agnès Mogenet, Laurent Frenzel, Gandhi Damaj, Olivier Lortholary, Olivier Hermine
JournalJournal of chromatography. B, Analytical technologies in the biomedical and life sciences (J Chromatogr B Analyt Technol Biomed Life Sci) Vol. 944 Pg. 175-81 (Jan 01 2014) ISSN: 1873-376X [Electronic] Netherlands
PMID24316764 (Publication Type: Journal Article)
CopyrightCopyright © 2013 Elsevier B.V. All rights reserved.
Chemical References
  • Staurosporine
  • midostaurin
Topics
  • Chromatography, Liquid (methods)
  • Drug Monitoring (methods)
  • Drug Stability
  • Humans
  • Linear Models
  • Mastocytosis, Systemic (drug therapy)
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Staurosporine (analogs & derivatives, blood, chemistry)
  • Tandem Mass Spectrometry (methods)

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