3PC-035 The stability of cyclophosphamide (CPA) and mesna mixture is shortened by cyclophosphamide instability causing quick PH decrease in solution

<h3>Background and Importance</h3> Cyclophosphamide (CPA) and mesna are commonly co-administered in oncological therapies to prevent bladder toxicity caused by metabolisation of CPA. Stability studies could allow the anticipated preparation of the mixture in centralised unit in hospital pharmacy. <h3>Aim and Objectives</h3> This study aims to evaluate the stability CPA/mesna mixture in polyolefin bags at 5°C and 25°C. <h3>Material and Methods</h3> CPA/mesna were prepared in polyolefin bags diluted in 0.9% sodium chloride at concentrations of 10/3.33 mg/mL (high concentration HC) and 1/0.33 mg/mL (low concentration LC). Samples were stored at 5°C and 25°C for 30 days. HPLC analysis for CPA and mesna were conducted at regular intervals alongside pH measurements, as well as visual inspections and osmolarity testing. pH was also assessed on solutions of CPA and mesna alone conserved at 25°C to evaluate their influence in the mixture. <h3>Results</h3> Osmolarity and visual examination showed great stability of the mixture over the 30 days period. The HPLC analysis showed active substance concentration fall under 90% of initial concentration from 8 days of conservation at 25°C or 14 days of conservation at 5°C. Notably, pH levels showed a steady decline in samples stored at 25°C, with a drop of more than 1 pH unit after 2 days. This decline was slightly slowed with 5°C conservation, with a drop superior to 1 unit which occurred between day 2 and day 8 of conservation for LC preparations. This decrease in pH occurred before any significant quantitative decrease of CPA or mesna in HPLC analysis, emphasising the critical role of pH monitoring in stability studies. Considering CPA and mesna solutions, a fast pH drop was only observed in CPA solutions over a 4 days period at 25°C. <h3>Conclusion and Relevance</h3> Because of pH drop, the shelf life of CPA/mesna mixtures should not be longer than 48 hours at 5°C conservation. The study underlines the importance of pH measurement for parenteral preparations, while pH instability could cause a preparation to be improper for intravenous administration. Interestingly, CPA stability studies which concluded 7 days conservation didn’t assed pH. New studies with exploration of pH could conclude to a shorter shelf life for CPA preparations. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest