An accelerated stability study of 5-flucytosine in intravenous solution.
The stability of the antimycotic drug flucytosine (5-FC) and the extent of 5-fluorouracil (5-FU) formation in 5-FC intravenous solution was studied in an accelerated stability experiment. 5-FC intravenous solution (10 mg/ml) was heated at 40, 60, 70, 80 and 90 degrees C for a maximum of 131 days. At appropriate time intervals samples were taken and the concentrations of 5-FC and 5-FU were determined using a newly developed, stability indicating HPLC-UV method. Heating the 5-FC intravenous solution at 40, 60, 70, 80 and 90 degrees C lead to 5-FC decomposition of respectively 0, 8.9, 14.4, 52.5 and 61.6%. The Arrhenius plot of the 5-FC decomposition is described by: Lnk5-FC decomposition = 80.1892 *1/T-0.2396 and the 5-FU formation is described by Lnk5-FU formation = -13087 *1/T + 34.4028. It is concluded that 5-FC is very stable in intravenous solution at regular storing temperatures and can therefore be stored at ambient temperatures for several years before the critical limit of 95% 5-FC is reached. However, the toxic and teratogen degradation product 5-FU may be present in considerable amounts in the product, due to both impurities in the raw material and the formation from 5-FC upon sterilisation and storage.
Vermes
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Department of Clinical Pharmacy, Academic Medical Center, University of Amsterdam, The Netherlands.
van der Sijs
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Guchelaar
H J
HJ
D000935:Antifungal Agents / Q000032:analysis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005437:Flucytosine / Q000032:analysis* / Q000737:chemistry; D005472:Fluorouracil / Q000032:analysis; D007262:Infusions, Intravenous; D019999:Pharmaceutical Solutions; D013056:Spectrophotometry, Ultraviolet; D013997:Time Factors
D000935:Antifungal Agents; D019999:Pharmaceutical Solutions; D005437:Flucytosine; D005472:Fluorouracil