Comparison of the limulus amebocyte lysate (LAL) test with the rabbit test: false positives and false negatives

Although the test for pyrogens on rabbits, described by the European Pharmacopoeia, is efficient for the detection of clinically important concentrations of pyrogens, it has some practical disadvantages; for instance, it blocks the further use of a rabbit for three weeks once this has been used to test a solution which proved to contain pyrogens. The LAL test for bacterial endotoxin lipopolysaccharides was explored as an alternative method for the detection of pyrogens in infusion fluids and medicinal preparations. False negatives in the LAL test were obtained on some corticosteroid preparations and on some infusion fluids from a batch which had caused febrile reactions in the clinic.