PB0014 - Extreme Long-term Stability of Aspirin Tablets and Their Ability to Inhibit Platelet Aggregation

Background: Now 125 years old, aspirin (acetylsalicylic acid) is most-commonly prescribed for its antiplatelet effect in the treatment/prevention of atherothrombotic events, including acute coronary syndromes. Aspirin is broken down by hydrolysis to salicylic acid (SA). Little information is available on the extreme long-term stability of aspirin formulations and their ongoing ability to inhibit platelet aggregation.

Aims: We characterised the extreme long-term biochemical stability and antiplatelet effect of aspirin tablets up to approximately 100 years old.

Methods: Plain aspirin tablets approximately 80 and 100 years old (Figure 1), as well as new stocks of aspirin and SA, were obtained and dissolved in saline. After assay optimisation, ultraviolet (UV) spectrophotometry against standard curves was used to quantify the current amounts of aspirin and SA in each formulation. To assess effects on platelet aggregation (PA), healthy volunteer blood was exposed to each preparation and light transmittance aggregometry performed using collagen (0.5 & 2mcg/mL) and arachidonic acid (AA, 1mmol/L) as agonists. Experiments were performed in quadruplicate.

Results: UV spectrophotometry performed on mixed solutions of new stocks demonstrated that concentrations (10-100micromol/L) of aspirin and SA could be accurately and specifically measured against a standard curve using absorbance at 290nm minus 230nm (aspirin), or 230nm alone (SA). Compared to new stock, tablets 80 and 100 years old had significantly lost aspirin content, with a corresponding increase in SA, but still contained 60.6+/-7.5% (mean+/-SD) and 40.2+/-3.5% of the original aspirin respectively (Figure 2). Formulations of both ages were still able to significantly inhibit collagen- and AA-induced PA when diluted equivalent to 10micromol/L-stock, though were weaker than new aspirin in inhibiting collagen-induced responses.

Conclusion(s): UV spectrophotometry is a convenient and accurate method to assess aspirin and SA content of tablets. In the extreme long-term, aspirin tablets retain significant antiplatelet activity. The half-life of active ingredient appears to be c.80-100 years.