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 vali dated for the determination of the antitumor agent depsipeptide (FR-901228) in plasma samples from patients with advanced cancer. After the plasma pro teins were precipitated with acetonitrile, the supernatant was extracted wi th ethylacetate. Depsipeptide was chromatographed on two serial octadecylsi lica stationary phases using a mobile phase consisting of acetonitrile-pota ssium phosphate buffer (0.03 M, pH 3) (27:73, v/v), at a flow-rate of 2.0 m l/min and at ambient temperature. The method was linear over a 50 to 2000 n g/ml range and the intra- and inter-day coefficients of variations were les s than 8%. The method was applied to the determination of the plasma concen tration-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) 19 98 Elsevier Science B.V. All rights reserved.