Stability Testing of Sirolimus in Medium-Chain Triglyceride Oil Using High-Performance Liquid Chromatography.

Abstract

Recently, a premature neonate, born at 26.5 weeks, was treated with sirolimus for kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon at the University of New Mexico Children's Hospital. Because of the lipophilic properties of the drug and an inability to draw the correct dose needed for the neonate with the standard 1 mg/mL concentration, sirolimus was diluted to 0.01 mg/mL (10 mg/L) in medium-chain triglyceride (MCT) oil. The objective of this study was to evaluate the stability of sirolimus diluted in MCT oil. Commercially available sirolimus oral solution was diluted with MCT oil from 1 mg/mL to 10 mg/L. The diluted samples were prepared by measuring 0.1 mL of the commercial product in an oral syringe and mixing with 9.9 mL of MCT oil. The 3 diluted samples were placed in amber glass vials, stored at 10°C, and analyzed over 14 days. The initial concentration of the 3 samples ranged from 8.5 to 10.8 mg/L sirolimus, or 85% to 108% of the target value. No significant differences were seen between average concentrations on the days tested. However, the average drug concentration fell to approximately 90% of the theoretical 10 mg/L target concentration between days 7 and 10. This study shows that sirolimus oral solution diluted with MCT oil to a final concentration of 10 mg/L was stable for at least 7 days when stored at 10°C, suggesting that the beyond-use date should be 7 days.