Methods for stabilizing 5-azacytidine in plasma

Chemistry: analytical and immunological testing – Heterocyclic carbon compound – Hetero-n

Reexamination Certificate

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C436S063000, C436S106000, C436S161000, C436S173000, C436S174000, C436S177000, C436S178000

Reexamination Certificate

active

10823394

ABSTRACT:
The invention provides methods for stabilizing 5-azacytidine against hydrolysis in plasma. By extracting the 5-azacytidine into acetonitrile and zinc sulfate, the 5-azacytidine can be stored for at least about 3 hours at about room temperature, and for at least about 4 days at about −70° C. If the acetonitrile is removed and evaporated to dryness, the 5-azacytidine in the resulting residue is stable for at least about 14 months at about −70° C. The invention also provides methods for determining the 5-azacytidine in acetonitrile, or in the acetonitrile residue, using, for example, high-performance liquid chromatography. The methods of the invention permit a significant time interval between the initial processing of the whole blood sample and the time of 5-azacytidine determination.

REFERENCES:
patent: 6943249 (2005-09-01), Ionescu et al.
J.A. Beisler (1978) J. Med. Chem. 21:204-208.
Kornblith et al. (2002) J. Clin. Oncol. 20:2441-2452.
Silverman et al. (2002) J. Clin. Oncol. 20:2429-2440.
Rustum & Hoffman (1987) J. Chromatog. 421:387-391.

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