Simultaneous determination of the new anticancer agent amidox and its metabolites in rat bile and plasma by high-performance liquid chromatography.
A new reversed-phase ion-pair high-performance liquid chromatography method was developed to study the first-pass hepatic metabolism of the anti cancer drug amidox in bile. Separation of the metabolites was achieved on a Spherisorb C18 column after liquid-liquid extraction using a linear gradient system of heptanesulfonic acid in potassium phosphate monobasic (pH 4.0) with increasing amounts of methanol (0-40%). The method was further applied to a pharmacokinetic study of amidox in rats after 200 mg kg-1 intraperitoneal administration. Using 50 microliters of rat bile and 300 microliters of rat plasma the limit of detection for amidox was 60 ng and 85 ng, respectively, and the assay was linear from 0.1 to 150 micrograms ml-1. This method appears to be sensitive enough to be used in further pharmacokinetic studies of amidox in human volunteers.
Vielnascher
E
E
Institute of Pharmaceutical Chemistry, University of Vienna, Austria.
Romanová
D
D
Novotný
L
L
Szekeres
T
T
Elfort
H L
HL
Thalhammer
T
T
Jäger
W
W
D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008297:Male; D010091:Oximes / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
D000970:Antineoplastic Agents; D010091:Oximes; C070491:Amidox