Kuijpers E A, den Hartigh J, Vermeij P
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, The Netherlands.
Pharm Dev Technol. 1998 May;3(2):185-92. doi: 10.3109/10837459809028494.
The stability of thiorphan (1.0 mg/ml) in normal saline containing 1% human serum albumin (HSA) was determined in order to find the most appropriate storage conditions. Direct liquid chromatographic analysis of this solution was feasible through the use of a micellar chromatographic system and proved to be stability indicating. During 8 weeks the percentages of the initial thiorphan concentration remaining after storage at 4, 20, 30, and 50 degrees C were determined. An Arrhenius plot was composed using the rate constants of thiorphan degradation at these temperatures. The thiorphan solution was stable for at least 2 months if stored at -20 degrees C. Taking into account the oxidative degradation of about 7% after thawing, we determined that the solution can be kept in a refrigerator for 4 days. Storage at room temperature should be limited to 1 day. By identification of the degradation products it could be concluded that thiorphan is degraded mainly via oxidation forming disulfides. Therefore, it is recommended that the solvent be purged with nitrogen before thiorphan is dissolved.
