High-performance capillary electrophoresis measurement of dolastatin-10.
A high-performance capillary electrophoresis (HPCE) assay was used to determine the concentration of a potent cytotoxic agent, dolastatin-10, in human plasma. Following extraction from plasma, using a solid-phase C18 cartridge, capillary zone electrophoresis was used to separate, detect and quantitate dolastatin-10 using the structurally related compound dolastatin-15 as the internal standard. Migration times for both dolastatins are less than 20 min. The recovery of the drug was approximately 90% and was quantified over the assay range of 39 to 5000 ng/ml with good precision and accuracy. The method is linear up to 5000 ng/ml with a lower limit of detection of 25 ng/ml. Data resulting from the use of the assay for the in vitro metabolism of the drug are presented. This is the first report of a validated HPCE assay for determining dolastatin-10 levels in human plasma.
Huie
W R
WR
Clinical Pharmacology Resource Facility, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Newman
R A
RA
Hutto
T
T
Madden
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood*; D047630:Depsipeptides; D019075:Electrophoresis, Capillary; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D009842:Oligopeptides / Q000097:blood*; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
D000970:Antineoplastic Agents; D047630:Depsipeptides; D009842:Oligopeptides; C064570:dolastatin 10