Determination of a new podophyllotoxin derivative, TOP-53, and its metabolite in rat plasma and urine by high-performance liquid chromatography with electrochemical detection.
A high-performance liquid chromatographic method was developed for the determination of a new podophyllotoxin derivative, TOP-53 (I), and TOP-53 glucuronide (II) as its major metabolite in rat plasma and urine. For the analysis of I, the sample was chromatographed on a reversed-phase C18 column with electrochemical detection after consecutive two-step liquid-liquid extractions. Compound II was determined as I after enzymatic hydrolysis of II. This method was validated sufficiently with respect to specificity, accuracy, and precision. The limits of quantitation for both I and II were 2 ng/ml in plasma and 10 ng/ml in urine. The method is thus useful for the pharmacokinetic study of I.
Kitamura
R
R
Pharmacokinetics Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Bandoh
T
T
Tsuda
M
M
Satoh
T
T
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004563:Electrochemistry; D005047:Etoposide / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D005965:Glucuronates / Q000097:blood / Q000652:urine; D051381:Rats; D012680:Sensitivity and Specificity
D000972:Antineoplastic Agents, Phytogenic; D005965:Glucuronates; C099874:TOP 53; C106025:TOP 53 glucuronide; D005047:Etoposide