Determination of the release of hydrolyzed demethylcantharidin from novel traditional Chinese medicine–platinum compounds with anticancer activity by gas chromatography

The present paper describes the development of a simple, accurate and reproducible gas chromatographic method for the determination of hydrolyzed demethylcantharidin release from a novel series of traditional Chinese medicine (TCM)–platinum compounds possessing potent anticancer and protein phosphatase 2A (PP2A)-inhibition properties. The salient features of the validated assay were a limit of detection (LOD) of 2 μg/mL, a limit of quantitation (LOQ) of 6 μg/mL, an intra- and inter-day precision of less than 11%, and an accuracy of more than 92%. The developed GC–flame ionization detection (FID) method was successfully utilized for the analysis of hydrolyzed demethylcantharidin, the TCM component that is slowly released from the novel compounds over 24 h, leading to PP2A inhibition. Further structural confirmation was achieved by GC–MS. The GC method is suitable for further mechanistic, pharmacokinetic and metabolic studies of the TCM–Pt compounds that might prove to be new anticancer agents with novel mechanisms of cytotoxic action.