Aims: Many nanoparticles interfere with traditional tests to quantify endotoxin. The aim of this study was to compare the performance of limulus amoebocyte lysate (LAL) formats on clinical-grade nanoformulations, to determine whether there were disparate results among formats and to test the applicability of an alternative bioassay (the macrophage activation test [MAT]) for resolving discrepancies, if observed.
Materials & methods: Clinical-grade nanoformulations were tested using turbidimetric, gel-clot and chromogenic LAL. Formulations that cause a discrepancy among LAL tests were also tested by the MAT.
Results & conclusion: The gel-clot LAL method cannot be relied upon to resolve discrepancies among LAL tests for certain nanoformulations. No one LAL format was shown to be optimal for all the tested clinical-grade nanoformulations. The tested alternative bioassay (the MAT) was useful for verifying LAL findings, but only for those nanoformulations not carrying/including cytotoxic drugs.
Keywords: endotoxin; in vitro assay; interference; limulus amoebocyte lysate; lipopolysaccharide nanoparticles; rabbit pyrogen test.