title: Validation of an HPLC method for analysis of DB-67 and its water soluble prodrug in mouse plasma.
abstract: 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 1-300ng/mL and 2.5-300ng/mL for the carboxylate and lactone, respectively (accuracy 90-110% of theory and coefficient of variation < or =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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Horn
authors.forename: Sherri L
authors.initials: SL
authors.lastname: Jordan
authors.forename: Lin
authors.initials: L
authors.lastname: Song
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Roberts
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Anderson
authors.forename: Markos
authors.initials: M
authors.lastname: Leggas
mesh_terms: D000818:Animals; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017646:Organosilicon Compounds / Q000097:blood* / Q000493:pharmacokinetics; D011355:Prodrugs / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence
chemical_list: D017646:Organosilicon Compounds; D011355:Prodrugs; C415575:7-tert-butyldimethylsilyl-10-hydroxycamptothecin; D002166:Camptothecin