Assessment of leachables in hospital pharmacy compounded topotecan conditioned in common off-label syringes for intravitreal use

Abstract

Compounding drug products is a vital hospital pharmacy feature that requires safe and compatible primary packaging, particularly for prefilled syringes (PFSs). The off-label use of plastic syringes in batch compounding for intravitreal administration has raised concerns over leachables and silicone oil lubricants, which may migrate into drug solutions and potentially cause toxicity. This study evaluated two widely used off-label plastic syringes, BD Plastipak and BBraun Omnifix, for conditioning with topotecan (TPT), a chemotherapeutic used to treat infant retinoblastoma. Leachables were monitored over 12 months via an original LC‒MS method with postcolumn infusion (PCI), including possible detection of silicone degradants. This approach may serve as an indirect method to assess silicone-related contamination due to the spread of free silicone particulates. Both syringes released low overall levels of leachables. However, BD Plastipak emits five oligomeric degradants, two exceeding permitted daily exposure (PDE) limits. In contrast, BBraun Omnifix showed greater chemical stability, releasing only minimal silicone-related compounds and oleamide, suggesting a lower risk for intraocular use. Although these findings support BBraun Omnifix as a safer option, the findings underscore the need for toxicologically assessed, purpose-designed plastic PFSs made from low-extractable materials such as cyclic olefin polymer (COP) or copolymer (COC) for long-term drug storage.