Physicochemical stability of dexmedetomidine diluted in 5% glucose solution in polypropylene syringes

Introduction
Dexmedetomidine is a selective α2-adrenergic receptor agonist increasingly used in neonatology because of its sedative properties and minimal respiratory depression. In neonates, sodium intake restrictions frequently require dilution in 5% glucose solution (G5%). However, no data have been reported regarding the stability of dexmedetomidine in this diluent, particularly at low concentrations.

Objective
To evaluate the physicochemical stability of dexmedetomidine diluted in G5% at concentrations of 0.4 µg/mL and 4 µg/mL, stored in polypropylene syringes under different temperature conditions.

Materials and methods
Two independent batches of dexmedetomidine were diluted in G5% to final concentrations of 0.4 and 4 µg/mL and packaged in polypropylene syringes. Preparations were stored for 28 days at 4 ± 2°C, 25 ± 2°C, and 40 ± 2°C. Drug concentrations were determined using high-performance liquid chromatography. The chromatographic conditions were : C18-HQ column (250 × 4.6 mm, 5 µm), mobile phase : acetonitrile/0.02 M phosphate buffer pH 3, (35:65, v/v), flow rate : 0.8 mL/min, and UV detection at 220 nm. Data were analyzed using Chromeleon® 7 software. Chemical stability was defined as a residual concentration ≥90% of the initial concentration. Visual inspection of the preparations was performed at each sampling time.

Results
At 4°C and room temperature, dexmedetomidine concentrations remained above 90% of the initial value up to day 21 for the 0.4 µg/mL solution and up to day 28 for the 4 µg/mL solution. At day 28, residual concentrations were 87.7% and 98.3% at 4°C, and 89.9% and 98.3% at room temperature for the 0.4 and 4 µg/mL solutions, respectively. At 40°C, a progressive decrease in concentration was observed from day 7 for both concentrations. The decrease followed a linear trend (R² = 0.983 and 0.994) and was more pronounced at the lower concentration, with regression slopes of −11.92%/day and −8.30%/day, respectively. At day 28, residual concentrations were 33.5% for the 0.4 µg/mL solution and 53.8% for the 4 µg/mL solution. No additional chromatographic peaks, visual changes, discoloration, or particle formation were observed throughout the 28-day study.

Conclusion
Dexmedetomidine diluted in G5% and stored in polypropylene syringes remained physicochemically stable for at least 21 days at 0.4 µg/mL and for at least 28 days at 4 µg/mL when stored at 4°C or room temperature. Stability was concentration-dependent, with more dilute solutions being less stable. At 40°C, a marked decrease in drug concentration was observed, highlighting the influence of temperature, with slightly greater sensitivity at the lower concentration. These findings support the feasibility of advance preparation in hospital pharmacy practice, provided that appropriate storage conditions are maintained.

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