Presence of Polycyclic Aromatic Hydrocarbons in Rubber Packaging Materials and in Parenteral Formulations Stored in Bottles With Rubber Stoppers.

Abstract

Rubber closures are the primary packaging material for sterile preparations intended for repeated use. Important features of rubber closures are achieved after additives are added to the elastomeric material that compounds the rubber. Among these additives is carbon black. Because of its origin, carbon black may contain polycyclic aromatic hydrocarbons (PAHs). The U.S. Environmental Protection Agency has identified 16 priority PAHs on the basis of concerns that they cause or might cause cancer in animals and humans. Regulatory agencies impose carbon black purity specifications based on limits for total PAHs (0.5 mg/kg) and benzo[a]pyrene (5 μg/kg) or benzo[a]pyrene only (250 μg/kg). PAHs in rubber packaging used for pharmaceutical formulations and in parenteral products stored in containers with rubber stoppers were investigated. To this end, the method proposed by the National Institute for Occupational Safety and Health-based on high-performance liquid chromatography with ultraviolet and fluorescence detection-was adapted to determine the levels of PAHs in rubber stoppers (gray and red) and in lipid emulsions and amino acid solutions stored in bottles with rubber stoppers. The rubber materials were shown to contain 12 PAHs, in concentrations ranging from 0.25-3.31 µg/g. Only 1 of 18 samples (11 amino acid solutions and 7 lipid emulsions) was uncontaminated. The most prevalent contaminants were pyrene, benzo[a]pyrene, and fluoranthene. The total PAH concentrations in the samples ranged from 0.11-5.96 µg/mL. Components of parenteral nutrition may be contaminated with PAHs, and rubber stoppers represent a potential source of these contaminants.