Removal of Escherichia coli lipopolysaccharides from electrolyte and non-electrolyte-containing parenteral solutions by ultrafiltration with cellulose triacetate membranes

Biocompatibility in parenteral therapy is now regarded as a multifactorial problem and large volume parenterals (LVPs) represent a main risk. Lipopolysaccharides (LPS) from Gram-negative bacteria are known to cause pyrogenic reactions in patients undergoing parenteral therapy. Removal of pyrogens from parenteral fluids continues to be a major regulatory concern. Ultrafilters are generally assumed to be impermeable to bacterial endotoxins contaminating LVPs used for parenteral therapy. The goal of the present study was to investigate the efficiency of cellulose triacetate ultrafilters in removing LPS from parenteral fluids. To evaluate the safety of cellulose triacetate membranes nine different parenteral fluids were spiked with various concentrations of E. coli lipopolysaccharides. After ultrafiltration endotoxin concentrations were measured using a chromogenic limulus amoebocyte lysate assay. This study indicated that cellulose triacetate ultrafiltration represents an efficient system to obtain endotoxin free parenteral fluids, when contaminated injectable solutions were passed through the membrane.