High-performance liquid chromatographic assay for the novel antitumor drug, bryostatin-1, incorporating a serum extraction technique.
An HPLC assay incorporating a solid-phase extraction technique has been devised for bryostatin-1. Quantitation of bryostatin was found to be linear over the concentration range 0.012-25 microg/ml (0.2-25 ng on column) 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 bryostatin over a range of concentrations from horse serum (0.012-25 microg/ml) and human serum (0.01-0.32 microg/ml) using a 100-mg C18 solid-phase extraction cartridge, extraction efficiencies consistently greater than 90% were obtained for extraction from horse serum and varied between 57 and 85% from human serum. However, on extending this work to blood samples from patients undergoing therapy with bryostatin-1, the drug was not detectable even at the maximum dose given, demonstrating the rapid loss of this agent from peripheral circulation.
Khan
P
P
CRC Department of Experimental Chemotherapy, Paterson Institute for Cancer Research, Christie CRC Cancer Centre, Manchester, UK.
McGown
A T
AT
Dawson
M J
MJ
Jayson
G
G
Prendiville
J A
JA
Pettit
G R
GR
Crowther
D
D
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood*; D054713:Bryostatins; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006736:Horses; D006801:Humans; D007783:Lactones / Q000008:administration & dosage / Q000097:blood*; D018942:Macrolides
D000970:Antineoplastic Agents; D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1