Physicochemical stability of adenosine at a clinically relevant intracoronary dose to induce hyperaemia

Since the physicochemical stability of adenosine at clinically relevant concentrations for intracoronary administration is unknown, the solution is typically prepared on site at the time of inducing hyperaemia, once the decision to measure fractional flow reserve for a stenosis is made during cardiac catheterisation. This additional preparation step contributes to both procedural and non-clinical delays and poses practical challenges. To address this gap, the present study evaluated the stability of adenosine admixed with two commonly used diluents stored at three different temperatures.

Adenosine (12 µg/mL) solutions were prepared by aseptic dilution of commercial adenosine injection (3 mg/mL) in 0.9% sodium chloride and 5% dextrose bags, transferred into sterile polypropylene syringes, and stored in the dark at 4°C, 25°C and 35°C for up to 49 days. Stability was assessed at predefined intervals using a validated stability-indicating high-performance liquid chromatography (HPLC) assay. Physical stability was monitored by pH measurement, visual inspection for colour change and microscopic evaluation of particulate matter.

Throughout the 49-day storage period, no visible particle formation, colour change or notable pH variation (greater than ±0.15 units) was observed in any of the samples. HPLC analysis confirmed that adenosine remained chemically stable, with more than 97% of the initial concentration retained in both diluents at all three storage temperatures.

Our findings support the prior preparation of adenosine for intracoronary administration in polypropylene syringes using 0.9% sodium chloride or 5% dextrose as diluents, with storage under tested conditions for up to 49 days. When required, the prepared syringes can be readily used during cardiac catheterisation. This approach would streamline workflow, minimise procedural delays and reduce the workload associated with on-site preparation.