Analysis of aplidine (dehydrodidemnin B), a new marine-derived depsipeptide, in rat biological fluids by liquid chromatography-tandem mass spectrometry

Aplidine (dehydrodidemnin B) is a new marine-derived depsipeptide with a po werful cytotoxic activity, which is under early clinical investigation in E urope and in the US. In order to investigate the pharmacokinetic properties of this novel drug, an HPLC-tandem mass spectrometry method was developed for the determination of aplidine in biological samples. Didemnin B, a hydr oxy analogue, was used as internal standard. After protein precipitation wi th acetonitrile and extraction with chloroform, aplidine was chromatographe d with a RP octadecylsilica column using a water-acetonitrile linear gradie nt in the presence of formic acid at the flow-rate of 500 mu l/min. The met hod was linear over a 5-100 ng/ml range (LOD=0.5 ng/ml) in plasma and over a 1.25-125 ng/ml range (LOD=0.2 ng/ml) in urine with precision and accuracy below 14.0%. The intra- and inter-day precision and accuracy were below 12 .5%. The extraction procedure recoveries for aplidine and didemnin B were 6 9% and 68%, respectively in plasma and 91% and 87%, respectively in urine. Differences in linearity, LOQ, LOD and recoveries between plasma and urine samples seem to be matrix-dependent. The applicability of the method was te sted by measuring aplidine in rat plasma and urine after intravenous treatm ent. (C) 1999 Elsevier Science B.V. All rights reserved.