An accelerated stability study of 5‐flucytosine in intravenous solution

Abstract

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 ∘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 ∘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.