Determination of the antitumor agent depsipeptide in plasma by liquid chromatography on serial octadecyl stationary phases

A high-performance liquid chromatographic assay has been developed and validated for the determination of the antitumor agent depsipeptide (FR-901228) in plasma samples from patients with advanced cancer. After the plasma proteins were precipitated with acetonitrile, the supernatant was extracted with ethylacetate. Depsipeptide was chromatographed on two serial octadecylsilica stationary phases using a mobile phase consisting of acetonitrile-potassium phosphate buffer (0.03 M, pH 3) (27:73, v/v), at a flow-rate of 2.0 ml/min and at ambient temperature. The method was linear over a 50 to 2000 ng/ml range and the intra- and inter-day coefficients of variations were less than 8%. The method was applied to the determination of the plasma concentration-time profile for 14 patients with advanced cancer receiving from 1 to 7.5 mg/m(2) of depsipeptide per day as a continuous 4-h infusion. (C) 1998 Elsevier Science B.V. All rights reserved.