HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY FOR THE NOVEL ANTITUMORDRUG, BRYOSTATIN-1, INCORPORATING A SERUM EXTRACTION TECHNIQUE

An HPLC assay incorporating a solid-phase extraction technique has bee n devised for bryostatin-l. Quantitation of bryostatin was found to be linear over the concentration range 0.012-25 mu g/ml (0.2-25 ng on co lumn) and was found to have a limit of detection of 0.2 ng on column, with a correlation coefficient of 0.9999. Following extraction of bryo statin over a range of concentrations from horse serum (0.012-25 mu g/ ml) and human serum (0.01-0.32 mu g/ml) using a 100-mg C-18 solid-phas e extraction cartridge, extraction efficiencies consistently greater t han 90% were obtained for extraction from horse serum and varied betwe en 57 and 85% from human serum. However, on extending this work to blo od samples from patients undergoing therapy with bryostatin-1, the dru g was not detectable even at the maximum dose given, demonstrating the rapid loss of this agent from peripheral circulation. (C) 1998 Elsevi er Science B.V.