Premium
Validation study of a method for assaying DE‐310, a macromolecular carrier conjugate containing an anti‐tumor camptothecin derivative, and the free drug in tumor tissue by high performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry
Author(s) -
Oguma Toshihiro,
Morikawa Hiroshi,
Iwasaki Daisuke,
Atsumi Ryo
Publication year - 2005
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.409
Subject(s) - conjugate , chemistry , camptothecin , chromatography , medicine , biochemistry , mathematics , mathematical analysis
DE‐310 is a macromolecular carrier conjugate containing an anti‐tumor camptothecin derivative, DX‐8951, which is conjugated to a water‐soluble polymer via a peptide spacer. Assay methods have been developed for the determination of a polymer‐bonded DX‐8951 conjugate, DX‐8951, and Glycyl‐DX‐8951 concentrations in murine Meth A tumor tissue. Free DX‐8951 and Glycyl‐DX‐8951 were extracted from tumor tissue homogenates by protein precipitation and analyzed by LC/MS/MS (method I). Conjugated DX‐8951 was isolated by solid‐phase extraction after digestion with a thermolysin. The productive phenylalanyl‐glycyl‐DX‐8951 was analyzed by LC/MS/MS (method II). The lower limits of quantitation of DX‐8951, Glycyl‐DX‐8951, and conjugated DX‐8951 were 1.36, 1.34 and 73.7 ng/g (as DX‐8951 equivalent). These two methods showed satisfactory sensitivity, precision and accuracy. To study the pharmacokinetics of DE‐310, it would be of great help to assay the polymer‐bonded DX‐8951 and its released drugs in tumor tissue. Copyright © 2004 John Wiley & Sons, Ltd.