Pyrogens in small-volume parenterals prepared in hospital pharmacy

Three pyrogen assay methods [the rabbit method, Limulus Amebocyte Lysate (LAL) gelation and chromogenic substrate, and bioburden prior to sterilization] were evaluated in three standard batches of small-volume parenteral preparations; i.e., water for injection, sodium chloride 0.9% injection, and sodium bicarbonate 8.4% injection. The same preparations were also assayed after contamination with Escherichia coli followed by sterilization. All methods gave the same results with the water for injection and the sodium chloride 0.9%. With sodium bicarbonate 8.4%, only the rabbit method was valid. For sodium chloride 0.9%, the chromogenic substrate method was valid; the gelation method was not valid. Endotoxins from the manufacturing plant were less pyrogenic in rabbits than were standard endotoxins or those from hospital E. coli.