Determination of the cyclic depsipeptide FK228, a histone deacetylase inhibitor, by liquid chromatography-mass spectrometry.

Abstract

An analytical method was developed for the quantitative determination of the novel histone deacetylase inhibitor, depsipeptide FK228 (formerly FR901228; NSC 630176), in human plasma. Calibration curves were constructed in the range of 0.5-100 ng/ml, and were analyzed using a weight factor proportional to the nominal concentration. Sample pretreatment involved a liquid-liquid extraction with ethyl acetate using 500 microl aliquots of plasma. The analyte was separated on a column (50 mm x 4.6 mm i.d.) packed with 3.5 microm C8 material, and eluted with methanol-10 mM ammonium formate (55:45; v/v; pH 8). The column effluent was monitored by mass spectrometry with electrospray ionization. The values for precision and accuracy were always < or =7.88% and <3.33% relative error, respectively. The method was successfully applied to examine the pharmacokinetics of FK228 in a cancer patient.

• Authors: Kyunghwa Hwang, Richard L Piekarz, Susan E Bates, William D Figg, Alex Sparreboom
• Journal: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences (J Chromatogr B Analyt Technol Biomed Life Sci) Vol. 809 Issue 1 Pg. 81-6 (Sep 25 2004) ISSN: 1570-0232 [Print] Netherlands
• PMID: 15282096 (Publication Type: Journal Article, Validation Study)

Chemical References

• Antibiotics, Antineoplastic
• Depsipeptides
• Enzyme Inhibitors
• Histone Deacetylase Inhibitors
• romidepsin

Topics

• Antibiotics, Antineoplastic (blood, pharmacokinetics)
• Calibration
• Depsipeptides (blood, pharmacokinetics)
• Enzyme Inhibitors (blood, pharmacokinetics)
• Histone Deacetylase Inhibitors
• Humans
• Reference Standards
• Reproducibility of Results