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

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 μl aliquots of plasma. The analyte was separated on a column (50 mm × 4.6 mm i.d.) packed with 3.5 μm 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 ≤7.88% and <3.33% relative error, respectively. The method was successfully applied to examine the pharmacokinetics of FK228 in a cancer patient.