Determination of intoplicine, a new antitumour drug, in human whole blood and plasma by normal-phase high-performance liquid chromatography with fluorescence detection.
Intoplicine, a benzopyrido-indole derivative, is a novel anticancer agent currently under phase I clinical evaluation. A selective, sensitive normal-phase high-performance liquid chromatographic (HPLC) assay with fluorescence detection, suitable for the determination of intoplicine in human plasma and whole blood, is described. The sample pretreatment involves a protein precipitation step with 2-propanol. The reported assay was validated, and the stability of the analyte in plasma, in whole blood and in the extraction fluid was investigated. The method has been implemented in a pharmacokinetic phase I clinical trial with intoplicine given as a 24-h intravenous infusion.
van Gijn
R
R
Slotervaart Hospital, Amsterdam, Netherlands.
Rosing
H
H
ten Bokkel Huinink
W W
WW
van Tellingen
O
O
Vermorken
J B
JB
Liefting
A J
AJ
Bruno
R
R
Pinedo
H M
HM
Beijnen
J H
JH
D000433:1-Propanol; D000970:Antineoplastic Agents / Q000097:blood*; D011232:Chemical Precipitation; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards / Q000706:statistics & numerical data; D004355:Drug Stability; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D007211:Indoles; D011725:Pyridines; D000433:1-Propanol; C081834:intoplicine