Determination of the cyclic depsipeptide FK228 in human and mouse plasma by liquid chromatography with mass-spectrometric detection

Xiaohong Chen, Erin R. Gardner, William D. Figg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

An analytical method was developed and validated for the quantitative determination of the cyclic depsipeptide FK228 (romidepsin, formerly FR901228; NSC 630176), a histone deacetylase inhibitor, in human and mouse plasma. Calibration curves were linear in the concentration range of 2-1000 ng/mL. Sample pretreatment involved a liquid-liquid extraction of 0.1 mL aliquots of plasma with ethyl acetate. FK228 and the internal standard, harmine, were separated on a Zorbax SB C18 column (75 mm × 2.1 mm, 3.5 μm), using a mobile phase composed of methanol and 0.2% formic acid. The column eluent was monitored by mass spectrometry with electrospray ionization. Accuracy and precision of four concentrations of quality control samples ranged from 101.5 to 106.4% and 0.7 to 3.5% in human plasma and 93.6 to 100.6% and 0.6 to 6.5%, in mouse plasma, respectively. This method represents a significant improvement over our previously published analytical assay for this agent, decreasing the sample volume requirements, increasing the accuracy and precision (through addition of a suitable internal standard), expanding the analytical range and validating in additional biological matrices. The developed method was applied to study the pharmacokinetics of FK228 in over 1000 clinical and preclinical samples.

Original languageEnglish
Pages (from-to)153-158
Number of pages6
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume865
Issue number1-2
DOIs
StatePublished - 1 Apr 2008
Externally publishedYes

Keywords

  • Depsipeptide
  • Human plasma
  • LC/MS
  • Mouse plasma

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