Human serum albumin-drug method

T. Hanai, Evaluation of measuring methods of human serum albumin-drug binding affinity, Curr. Pharm. Anal, 2007, 3, 205-212. 

Table 18 Human serum albumin-drug binding affinity and drug properties. rrSTi represents log k measured using an immobilized-HSA phase. nKa represents predicted log hsa-represents log k of acidic compounds at pH 7.4. k represents log k of basic compounds at pH 7.4. MIFa and MIFb represents the molecular interaction energy values of acidic and basic compounds, resepectively. nKs represents log nST measured using a modified Hummel-Dreyer method. nJQ, nKs, nSTg and nKj represent values. PB and PB2 represent the binding %. Log Pc are predicted log P values, and log Pm are measured values. 7.4 represents pH 7.4. Reproduced by permission of Bentham Science, ref. 20.

Several methods for measuring drug binding to human serum albumin involving the determination of retention times on HPLC columns with bound albumin have been reported [77,78]. Solid-phase microextraction [79,80], capillary electrophoresis [81], and displacement of near-infrared fluorescent labels [82] have all been studied. 

Kraak et al. (38) reported the first ACE application to study drug binding to a plasma protein. They used the model system warfarin-human serum albumin (HSA) to compare the suitability of the Hummel-Dreyer, frontal analysis, and vacancy peak methods. A more methodologically intended paper from Erim and Kraak (39) used VACE to study the displacement of warfarin from bovine serum albumin (BSA) by furosemide and phenylbutazone. They concluded that VACE is especially suited to examining competitive properties of simultaneously administered compounds toward a given protein-drug system. 

Tiller, P. R. Mutton, I. M. Lane, S. J. Bevan, C. D. 1995. Immobilized human serum albumin liquid chromatography/mass spectrometry as a method of determining drug-protein binding. Rapid Commun. Mass Spectrom., 9,261-263. 

Many compounds bind to human serum albumin (HSA), which significantly reduces their in vivo activity and hence their potential as a drug lead. The fragmentation method has recently been used to find analogs of diflusinal (29) that have a reduced affinity toward HSA... 

Protein interactions have been investigated by ITP (D6). It has, for example, been possible to determine the number of sodium dodecyl sulfate (SDS) molecules bound to bovine serum albumin (H14, H15) and to investigate the binding of drugs such as indomethacin to human serum albumin (H15). This method could be of value in pharmacokinetic studies. 

Lin W, Coombes A, Davies M, Davis S, Ilium L, (1993). Preparation of Sub-100 nm Human Serum Albumin Nanospheres Using a pH-Coacervation Method. Journal of Drug Targeting, 1(3), 237-243. Soppimath K.S, Aminabhavi T.M, Kulkami A.R, Rudzinski W.E. (2001) Biodegradable polymeric nanopaiticles as drug delivery devices. Journal of Controlled Release, 70(1-2), 1-20. 

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