Pharmaceutical stability of compounded acetylcholine chloride intraocular solution for intracoronary provocative...

Provocative coronary vasospasm testing requires intracoronary acetylcholine (ACh) administration, however an ACh drug formulation approved for intracoronary use is not commercially available. Invasive coronary vasomotor testing programs have thus resorted to reconstituting and diluting ophthalmic ACh solutions for off-label and off-target intracoronary use, despite a lack of comprehensive ACh stability testing data required by pharmacy compounding regulations USP <797 > . This study aims to characterize the stability of compounded ACh intraocular solutions according to current pharmacy guidelines for use in provocative intracoronary ACh vasospasm testing.

Potency and stability testing was performed by an FDA and DEAS registered, A2LA ISO 17025:2017 accredited laboratory. Using a simple, 7-step compounding method, a single vial of intraocular ACh solution was reconstituted and diluted with 500 mL of dextrose 5% water (D5W) to a final concentration of 18.2 mcg/mL. Compounded ACh was then stored in 20 mL syringes at ambient room temperature (25 ± 2 °C and 60 ± 5% relative humidity) under normal fluorescent lighting to simulate routine cardiac catheterization laboratory conditions. The compounded ACh solution appearance, pH, particulate matter, concentration and potency were evaluated in triplicate at 0, 4, and 12 h after compounding.

The compounded ACh solution was clear and colorless with a pH of 4.2 across all time points. Subvisible particulate matter, assessed by light obscuration techniques, demonstrated that the quantity of >10 μm and >25 μm particles present in each syringe remained safely within USP <788 > specifications. Finally, using high-performance liquid chromatography - mass spectrometry, the compounded ACh solutions revealed no significant degradation during the studied time frame, with 96.7 ± 0.3% of the initial ACh retained at 12 h, satisfying USP <797 > regulations to maintain 90.0% - 110.0% of label claim (18.2 mcg/mL).

Utilizing a novel compounding method, intraocular ACh reconstituted and diluted in D5W met all USP <797 > pharmacy stability regulatory criteria over 12 h under ambient room temperature storage conditions. This study thus establishes a simplified ACh compounding approach for invasive coronary function testing centers to generate an intracoronary ACh drug formulation for use within 12 h in provocative coronary vasospasm testing procedures.