Metabolite profiling of the novel anti-cancer agent, plitidepsin, in urine and faeces in cancer patients after administration of ¹⁴C-plitidepsin.

Blood samples were drawn and excreta were collected until less than 1% of the administered radioactivity was excreted per matrix for two consecutive days. Samples were pooled within-patients and between-patients and samples were screened for metabolites. Afterwards, metabolites were identified and quantified. Analysis was done using Liquid Chromatography linked to an Ion Trap Mass Spectrometer and offline Liquid Scintillation Counting (LC-Ion Trap MS-LSC).

Plitidepsin is extensively metabolised and it undergoes dealkylation (demethylation), oxidation, carbonyl reduction, and (internal) hydrolysis. The chemical formula of several metabolites was confirmed using high resolution mass data.

On average 4.5 and 62.4% of the administered dose was excreted via urine over the first 24 h and in faeces over 240 h, respectively. Most metabolites were found in faeces.

Plitidepsin absorption, distribution, metabolism and excretion characteristics were investigated in a mass balance study, in which six patients received a 3-h intravenous infusion containing 7 mg ¹⁴C-plitidepsin with a maximum radioactivity of 100 µCi.