Chemical stability and adsorption of atracurium besylate injections in disposable plastic syringes

Abstract

Atracurium besylate (AB) is supplied as a sterile, non-pyrogenic aqueous solution for intravenous use. Hospitals pre-fill disposable plastic syringes with these solutions so that they are ready for immediate use when required. Drug loss due to potential adsorption on to the plastic material of the syringes has not been studied. Atracurium is also administered by intravenous infusion using a diluted solution in either 5% dextrose injection (USP) or 0.9% sodium chloride injection USP. Drug solutions not used within 24 h are usually discarded, resulting in tremendous waste. The purpose of these investigations was to determine the adsorption behaviour of atracurium when stored in plastic syringes, and to study the degradation of atracurium in i.v. fluids. For the adsorption study, 10 mg/ml solutions were used, whereas the diluted infusion solutions were prepared to contain 0.5 mg/ml of atracurium. Drug degradation was monitored using a stability-indicating high-performance liquid chromatography method. Degradation studies were conducted at 5 degrees C, 25 degrees C and 40 degrees C. Refrigeration was observed to improve drug stability. The manufacturer's recommended expiry period was too conservative. Storage at room temperature for up to 6 weeks can be safely recommended, without significant loss of chemical stability.