Liquid chromatographic assays for DE-310, a novel camptothecin analog, and two major enzymatic products in human matrices.
Assays were developed for determination of DE-310, a carboxymethyldextran polyalcohol conjugate of the topoisomerase I inhibitor DX-8951 (exatecan) and two enzymatic products (i.e. glycyl-DX-8951 and unconjugated DX-8951) in human whole blood, erythrocytes and saliva. Sample pretreatment involved a single protein-precipitation step, followed by a thermolysin-mediated deconjugation for the parent molecule. Separation of the compounds was achieved on an Inertsil ODS-80A column (150 mm x 4.6 mm i.d.; 5 microm PS), using isocratic elution. The column effluent was monitored at excitation and emission wavelengths of 375 and 445 nm, respectively. Validation results indicated that the methods are accurate and precise at lower limits of quantitation of 0.5-6.9 ng/ml. The methods were used to study the blood distribution and salivary concentrations in patients receiving DE-310.
Soepenberg
Otto
O
Laboratory of Translational and Molecular Pharmacology, Department of Medical Oncology, Erasmus University Medical Center--Daniel den Hoed Cancer Center, 3008 AE Rotterdam, The Netherlands. o.soepenberg@erasmusmc.nl
de Bruijn
Peter
P
Verweij
Jaap
J
Atsumi
Ryo
R
Sparreboom
Alex
A
D002138:Calibration; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004912:Erythrocytes / Q000737:chemistry; D006801:Humans; D012015:Reference Standards; D015203:Reproducibility of Results; D012463:Saliva / Q000737:chemistry*; D012680:Sensitivity and Specificity
C452060:DE-310 cpd; D002166:Camptothecin