Analysis of aplidine (dehydrodidemnin B), a new marine-derived depsipeptide, in rat biological fluids by liquid chromatography-tandem mass spectrometry.
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Celli N, Gallardo AM, Rossi C, Zucchetti M, D'Incalci M, Rotilio D
Analysis of aplidine (dehydrodidemnin B), a new marine-derived depsipeptide, in rat biological fluids by liquid chromatography-tandem mass spectrometry.
J Chromatogr B Biomed Sci Appl. 1999 Aug 20;731(2):335-43.
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- 10510788 [ View in PubMed]
- Abstract
Aplidine (dehydrodidemnin B) is a new marine-derived depsipeptide with a powerful cytotoxic activity, which is under early clinical investigation in Europe 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 hydroxy analogue, was used as internal standard. After protein precipitation with acetonitrile and extraction with chloroform, aplidine was chromatographed with a RP octadecylsilica column using a water-acetonitrile linear gradient in the presence of formic acid at the flow-rate of 500 microliters/min. The method 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 69% 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 tested by measuring aplidine in rat plasma and urine after intravenous treatment.
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