Stability-indicating LC assay of and impurity identification in homoharringtonine samples

Homoharringtonine (HHT) is a potent myelosuppressive agent and has antitumo r activity. Recent studies suggest that it inhibits tumor growth by inducin g apoptosis. HHT is an ester of the alkaloid cephalotaxine. It is isolated from genus Cephalotaxus. At least ten HHT analogs have been identified from cephalotaxus extracts. High performance liquid chromatography (HPLC) separ ations of the cephalotaxine alkaloids in plant extracts have been reported, they have not been validated as specific and stability-indicating for HHT. Due to the complexity of the alkaloid extracts, it is conceivable that add itional analogs may still be unresolved from HHT. This paper presents an im proved and validated HPLC assay for HHT. The assay is stability-indicating, precise (R.S.D. < 1%), linear (r(2) = 0.9999), and accurate (error < 1%). The assay reveals three congeners present as impurities in HHT samples. Two are new and have not been previously reported. Identities of the impuritie s and forced decomposition products, elucidated with their HPLC retention a nd spectral data, are also presented. (C) 2000 Elsevier Science B.V. All ri ghts reserved.