Analysis of anticancer drugs in biological fluids: determination of taxol with application to clinical pharmacokinetics.
Taxol, a novel antimitotic, antitumor agent is currently undergoing Phase 1 clinical trials for the treatment of various tumors. An isocratic HPLC method has been developed for the determination of taxol in human plasma and urine. The method was then applied to the clinical pharmacokinetics of taxol following 6-h intravenous (i.v.) infusions at doses of 175 and 225 mg m-2. A mobile phase of methanol-acetate buffer (0.02 M, pH 4.5) (65:35, v/v) was used to elute a C8 column with detection at 227 nm. The sample preparation involved extraction with t-butyl methyl ether followed by further clean-up of the sample by solid-phase extraction. The method was linear from 0.10-10 microM injected, with a chromatographic run time of 6 min. The results obtained from the clinical study indicate that the plasma pharmacokinetics of taxol are best characterized by a two compartment open body model. Additionally, the present study resulted in the detection of a previously unreported peak which may be a metabolite of taxol.
Rizzo
J
J
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045-2504.
Riley
C
C
von Hoff
D
D
Kuhn
J
J
Phillips
J
J
Brown
T
T
D000470:Alkaloids / Q000032:analysis* / Q000493:pharmacokinetics; D000972:Antineoplastic Agents, Phytogenic / Q000032:analysis* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D017239:Paclitaxel
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel