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 H PLC-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: Ln k(5-FC decomposition) = 80.1892 * 1/T - 0.2396 and the 5-FU formation is de scribed by Lnk(5-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 f or 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 conside rable amounts in the product, due to both impurities ih the raw material an d the formation from 5-FC upon sterilisation and storage.