| Autor: |
Guo D; College of Pharmacy, University of Arizona, 1703 East Mabel, Tucson, Arizona, USA. guod@pharmacy.arizona.edu, Myrdal PB, Karlage KL, O'Connell SP, Wissinger TJ, Tabibi SE, Yalkowsky SH |
| Jazyk: |
angličtina |
| Zdroj: |
AAPS PharmSciTech [AAPS PharmSciTech] 2010 Mar; Vol. 11 (1), pp. 247-52. Date of Electronic Publication: 2010 Feb 12. |
| DOI: |
10.1208/s12249-010-9383-2 |
| Abstrakt: |
In vivo, the DNA methyltransferase inhibitor, 5-fluoro-2'-deoxycytidine (FdCyd, NSC-48006), is rapidly converted to its unwanted metabolites. Tetrahydrouridine (THU, NSC-112907), a cytidine deaminase inhibitor can block the first metabolic step in FdCyd catabolism. Clinical studies have shown that co-administration with THU can inhibit the metabolism of FdCyd. The National Cancer Institute is particularly interested in a 1:5 FdCyd/THU formulation. The purpose of this study was to investigate the in vitro pH stability of FdCyd and THU individually and in combination. A stability-indicating high-performance liquid chromatography method for the quantification of both compounds and their degradants was developed using a ZIC(R)-HILIC column. The effect of THU and FdCyd on the in vitro degradation of each other was studied as a function of pH from 1.0 to 7.4 in aqueous solutions at 37 degrees C. The degradation of FdCyd appears to be first-order and acid-catalyzed. THU equilibrates with at least one of its degradants. The combination of FdCyd and THU in solution does not affect the stability of either compound. The stability and compatibility of FdCyd and THU in the solid state at increased relative humidity and at various temperatures are also evaluated. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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