OBJECTIVES: ketamine or dexmedetomidine to oxycodone affects the microbiological, physical or chemical stability of patient-controlled analgesia (PCA) solutions prepared in a hospital pharmacy. METHODS: ketamine mixtures (0.25, 0.50, 0.75 mg/mL) and three oxycodone-dexmedetomidine mixtures (2.5, 5.0, 10 µg/mL) were compounded under validated European Union Good Manufacturing Practice (GMP) Class A/B aseptic conditions and filled into PCA reservoirs. Reservoirs (n=42 for physicochemical studies, n=21 for sterility, n=4 for antimicrobial activity testing) were stored at 2-8°C for 28 days, then at 20-25°C for 2 days. Sterility was assessed by membrane filtration according to European Pharmacopoeia Section 2.6.1 (Ph. Eur. 2.6.1). Physical stability was evaluated by visual inspection, pH, weight and osmolality. Chemical stability was assessed using a validated high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method developed in accordance with US Food and Drug Administration (FDA) and International Conferenece on Harmonisation (ICH) Q2(R1) guidelines. RESULTS: ketamine and dexmedetomidine concentrations remained within ±5% of initial values, and no degradation products were detected. CONCLUSIONS: ketamine or dexmedetomidine remained sterile, physically stable and chemically stable for 28 days at 2-8°C followed by 2 days at room temperature at 20-25°C. These findings support the potential for extended shelf life and centralised batch preparation of opioid-adjuvant PCA reservoirs in hospital pharmacy practice.
Vaisanen et al. (Wed,) studied this question.