| Autor: |
Cummings, Jeffrey, French, Raymond, MacLellan, Alex, Smyth, John, Cummings, J, French, R C, MacLellan, A, Smyth, J F |
| Zdroj: |
Cancer Chemotherapy & Pharmacology; Jan1991, Vol. 28 Issue 1, p27-32, 6p |
| Abstrakt: |
GR63178A is the second pentacyclic pyrroloquinone to enter clinical trials as an anticancer drug. We developed a reversed-phase, gradient-elution high-performance liquid chromatography (HPLC) method along with a Bond Elut C2 mini-column sample-preparation technique for the analysis of GR63178A, its 9-hydroxy-metabolite GR54374X and internal standard GR70440A in human plasma and urine. The limit of detection is 2 ng/ml for both GR63178A and GR54374X. Analysis of GR63178A is complicated by its light instability, whereby a number of chromatographically distinct, stable degradation products can form. These can be practically eliminated if clinical specimens are frozen immediately and all subsequent sample preparation is performed in a darkroom. Using this methodology, a total of six metabolites (including GR54374X) were detected in human plasma and urine specimens. The five new metabolites were characterised according to polarity (HPLC retention time), UV-visible absorption maxima and the effect of incubation with beta-glucuronidase and aryl-sulphatase. Application of this methodology to the analysis of GR63178A will aid in the development of this novel synthetic anticancer drug. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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