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Artigo em Inglês | MEDLINE | ID: mdl-15734166

RESUMO

DE-310 is a macromolecular carrier conjugate containing an anti-tumor camptothecin derivative, DX-8951, conjugated to a water-soluble polymer by means of a peptide spacer. New assay methods have been developed to determine the polymer-bonded DX-8951 conjugate, free DX-8951, and Glycyl-DX-8951 in human plasma. Solid-phase extraction was used to extract free DX-8951 and Glycyl-DX-8951 from plasma, and LC/MS/MS (Method I) was used to determine the amount of each analyte. Protein precipitation was used to extract Conjugated DX-8951, which was then digested with thermolysin. HPLC (Method II) was used to determine the productive compound (Phenylalanyl-Glycyl-DX-8951). The lower limit of quantitation of DX-8951 was 50 pg/ml, of Glycyl-DX-8951 was 80 pg/ml, and of Conjugated DX-8951 was 100 ng/ml (as DX-8951 equivalent). Both methods showed satisfactory sensitivity, precision, and accuracy.


Assuntos
Antineoplásicos/sangue , Camptotecina/análogos & derivados , Camptotecina/sangue , Cromatografia Líquida de Alta Pressão/métodos , Camptotecina/isolamento & purificação , Cromatografia Líquida/métodos , Estabilidade de Medicamentos , Humanos , Espectrometria de Massas/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Termolisina
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