Validation of an LC–MS/MS method for simultaneous detection of four HDAC inhibitors – belinostat, panobinostat, rocilinostat and vorinostat in mouse plasma and its application to a mouse pharmacokinetic study

Kalpesh Kumar Giri, P. S. Suresh, Syed Mohd Saim, Mohd Zainuddin, Ravi Kanth Bhamidipati, Purushottam Dewang, Mahanandeesha S. Hallur, Sridharan Rajagopal, Sriram Rajagopal, Ramesh Mullangi*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

A sensitive and rapid LC–MS/MS method was developed and validated for the simultaneous quantitation of four HDAC inhibitors, namely belinostat (BST), panobinostat (PST), rocilinostat (RST) and vorinostat (VST), in mouse plasma as per regulatory guidelines. The analytes and internal standard were extracted from 50 μL mouse plasma by protein precipitation, followed by chromatographic separation using an Atlantis C18 column with an isocratic mobile phase comprising 0.1% formic acid–acetonitrile (25:75, v/v) at a flow rate of 0.5 mL/min within 2.5 min. Detection and quantitation were done by multiple reaction monitoring on a triple quadrupole mass spectrometer following the transitions: m/z 319 → 93, 350 → 158, 434 → 274 and 265 → 232 for BST, PST, RST and VST, respectively, in the positive ionization mode. The calibration curves were linear from 2.92 to 2921 ng/mL for BST and PST and from 1.01 to 1008 ng/mL for RST and VST with r2 ≥ 0.99 for all of the analytes. The intra- and inter-batch accuracy and precision (CV) across quality controls varied from 85.5 to 112% and from 2.30 to 12.5, respectively, for all of the analytes. Analytes were found to be stable under different stability conditions. The method was applied to an i.v. pharmacokinetic study in mice.

Original languageEnglish
Article numbere3912
Number of pages12
JournalBiomedical Chromatography
Volume31
Issue number7
DOIs
Publication statusPublished - 1 Jul 2017
Externally publishedYes

Keywords

  • belinostat
  • LC–MS/MS
  • method validation
  • mouse plasma
  • panobinostat
  • pharmacokinetics
  • rocilinostat
  • vorinostat

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