The Analysis of Apomorphine Formulations for Ambulatory Infusions

Abstract

An HPLC assay has been developed for the specific determination of apomorphine hydrochloride in ambulatory infusions. This assay was able to resolve a degradation peak of apomorphine which rapidly formed under the acidic conditions commonly used in liquid-liquid extraction procedures for apomorphine, as well as in alkaline conditions. The adduct formed from the reaction of apomorphine with sodium metabisulphite was also separated in this assay. The presence of a chelating agent (EDTA, 0·003% w/v) in the mobile phase prevented interference by secondary degradation products postulated to be formed by M2+-catalysed auto-oxidation of degraded apomorphine on the HPLC system. Apomorphine injection (10 mg mL−1) (Manor Park Pharmaceuticals, formulated with EDTA, 0·05% w/v, and ascorbic acid, 0·1% w/v) was found to be unstable over a 7-day incubation period in Graseby 9000 series infusion reservoir cassettes, both at 8 and 37°C, with drug solutions rapidly darkening over time, pH values lowering, and unpleasant odours developing, although the measured apomorphine concentrations did not significantly alter. However, apomorphine injection (10 mg mL−1) from Brittania Pharmaceuticals (formulated with sodium metabisulphite, 0·1% w/v) did not show any colour or pH changes under the same incubation conditions, with 98% remaining after 14 days at 8°C, and 96% remaining after 7 days at 37°C. The Britaject formulation could therefore be recommended for use in the Graseby 9000 series infusion device.