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 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.