Absence in amphotericin B-spiked human plasma of the free monomeric drug, as detected by SERS

Using surface enhanced Raman spectroscopy (SERS) which enables us to specif ically detect traces of monomeric amphotericin B (AmB), we were able to sho w that in a 10(-5) M AmB suspension, the concentration of free drug was bel ow 10(-8) M in the presence of low density lipoproteins (LDL) or plasma, Th e affinity constant of AmB for LDL determined from electronic absorption da ta, was found to be 4 x 10(6) M-1. Therefore, since AmB appears to be in th e majority bound to lipoproteins under in who conditions, its toxicity shou ld not result from the induction of host-cell transmembrane permeability bu t rather from the internalization of the AmB-LDL complex. (C) 1999 Federati on of European Biochemical Societies.