Validation of an HPLC method for analysis of DB-67 and its water soluble prodrug in mouse plasma

摘要

A method for the quantitation of DB-67 ((20S)-10-hydroxy-7-tert-butyldimethylsilylcamptothecin) lactone and carboxylate in mouse plasma has been developed, validated, and applied in pharmacokinetic studies. The analytes were separated by reversed-phase chromatography with fluorescence detection. Validation demonstrated the selectivity and specificity for the carboxylate and lactone, with linearity between 1-300 ng/mL and 2.5-300 ng/mL for the carboxylate and lactone, respectively (accuracy 90-110% of theory and coefficient of variation <= 5.7%). Carboxylate to lactone conversion was < 4% using this method. The assay was found to be suitable for the analysis of DB-67 lactone and carboxylate in pharmacokinetic studies following intravenous administration of DB-67 or its delta-aminobutyric acid ester derivative. (c) 2006 Elsevier B.V. All rights reserved.