Background Mixing different drugs for use in continuous infusion systems is a common practice in palliative care, but the analytical study of compatibility and stability is not always available.
Purpose To evaluate the compatibility and stability of two admixtures of ondansetron and haloperidol at different temperatures (25°C, 37°C). The concentrations of the admixtures are: 0.15 mg/ml – 0.25 mg/ml and 0.3 mg/ml – 0.4 mg/ml of haloperidol and ondansetron respectively in NaCl 0.9% stored in elastomeric infusors protected from light.
Material and methods The samples were prepared and diluted in NaCl 0.9% in elastomeric infusors in triplicate to obtain four different conditions of concentration and/or temperature of storage (concentration: 0.15 mg/ml – 0.25 mg/ml and 0.3 mg/ml – 0.4 mg/ml of haloperidol and ondansetron respectively: temperature of storage 25°C and 37°C).
The concentration of each constituent drug into different mixtures was periodically determined using a HPLC-UVmethod. The drugs were chromatographed on a C18 reverse phase column: the mobile phase was methanol:KH2PO40.05 M, adjusted to pH 3 with H3PO3 (60:40, v/v) delivered at a flow rate of 1.0 mL min-1. The sample injection volume was 20 µL, and triplicate injections were performed for every sample. The signal was recorded during 8 min and the retention times were 3.6 min for ondansetron and 6.6 min for haloperidol. Ondansetron and haloperidol concentrations were determined at 254 nm by interpolation from the calibration curves prepared from the standards. The Statgraphics centurion XVI program has been used for data treatment.
Results All solutions were initially clear and colourless but visible particles appear, in all cases, in the infusers after 2 days since their preparation. Chemical stability of the admixtures diluted in NaCl 0.9% are as follows: haloperidol-ondansetron (0.15 mg/ml – 0.25 mg/ml) is stable (retained >90% of their initial concentration) 2 days at 25°C and 37°C; and (0.3 mg/ml 0.4 mg/ml) is stable two days at 25°C and 37°C.
Conclusion The mixture of haloperidol and ondansetron stored in infusor devices is not stable because visible particles appear in less than 48 hours. Physical pressure by the elastomeric infusor may have a role in the instability, since precipitate is not appreciated when stored in flasks.
No conflict of interest
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