High-performance liquid chromatographic method for the simultaneous determination of the camptothecin derivative irinotecan hydrochloride, CPT-11, and its metabolites SN-38 and SN-38 glucuronide in rat plasma with a fully automated on-line solid-phase extraction system, PROSPEKT.
We established a high-performance liquid chromatography (HPLC) method for the simultaneous determination of the camptothecin (CPT) derivative, irinotecan hydrochloride (CPT-11) and its metabolites, 7-ethyl-10-hydroxycamptothecin (SN-38) and SN-38 glucuronide (SN-38G) in rat plasma with a fully automated on-line solid-phase extraction system, PROSPEKT. Plasma samples were pretreated with 0.146 M H3PO4 to inactivate carboxylesterase and beta-glucuronidase in rat plasma, and added with the internal standard solution (0.146 M H3PO4 containing 1 microgram/ml CPT) and then analyzed. The method was validated for CPT-11 (5 to 25,000 ng/ml), SN-38 (5 to 2500 ng/ml) and SN-38G (2.5 to 500 ng/ml). This method enabled the determination of many samples within a relatively short time with easy sample preparation. It also had four advantages compared with conventional determination methods, i.e. automation of a complicated sample preparation, time-saving by the simultaneous determination of three compounds, the direct determination of SN-38G, and the small amount of plasma required for the determination.
Kurita
A
A
Yakult Central Institute for Microbiological Research, Tokyo, Japan.
Kaneda
N
N
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood*; D002138:Calibration; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D004355:Drug Stability; D005965:Glucuronates / Q000097:blood*; D000077146:Irinotecan; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013050:Spectrometry, Fluorescence
D000972:Antineoplastic Agents, Phytogenic; D005965:Glucuronates; D000077146:Irinotecan; D002166:Camptothecin