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 t he simultaneous determination of the camptothecin (CPT) derivative, irinote can hydrochloride (CPT-11) and its metabolites, 7-ethyl-10-hydroxycamptothe cin (SN-38) and SN-38 glucuronide (SN-38G) in rat plasma with a fully autom ated on-line solid-phase extraction system, PROSPEKT. Plasma samples were p retreated with 0.146 M H3PO4 to inactivate carboxylesterase and beta-glucur onidase in rat plasma, and added with the internal standard solution (0.146 M H3PO4 containing 1 mu g/ml CPT) and then analyzed. The method was valida ted 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 withi n a relatively short time with easy sample preparation. It also had four ad vantages compared with conventional determination methods, i.e. automation of a complicated sample preparation, time-saving by the simultaneous determ ination of three compounds, the direct determination of SN-38G, and the sma ll amount of plasma required for the determination. (C) 1999 Elsevier Scien ce B.V. All rights reserved.