title: Human serum albumin-modified Fe3O4 magnetic nanoparticles for affinity-SALDI-MS of small-molecule drugs in biological liquids.
abstract: Here, we report on the use of human serum albumin (HSA)-modified Fe(3)O(4) nanoparticles (NPs) (HSA-Fe(3)O(4) NPs) for affinity-SALDI-MS of small drugs in human biological liquids. We demonstrated that HSA-Fe(3)O(4) NPs effectively captured small drugs from human urine and serum via the interactions between HSA and these drugs. The drugs adsorbed on HSA could then be identified by directly introducing the HSA-Fe(3)O(4) NPs into a mass spectrometer for SALDI-MS analysis. The ability of HSA to interact with multiple small drugs facilitated the simultaneous detection of a 4-drug-mixture in serum, viz., phenytoin, ibuprofen, camptothecin, and warfarin sodium, by affinity-SALDI-MS using HSA-Fe(3)O(4) NPs. In contrast, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) with an organic matrix could detect only warfarin sodium. We also demonstrated the capacity of affinity-SALDI-MS to quantify warfarin sodium in urine samples across a range of 50 - 1000 μM (R(2) = 0.998) when using HSA-Fe(3)O(4) NPs. The detection sensitivity was further improved to a range of 5 - 100 μM (R(2) = 0.999) by using denatured HSA. The open structure of denatured HSA may enhance the effective extraction of small drugs from biological liquids, and increase the detection-sensitivity of affinity-SALDI-MS. Affinity-SALDI-MS using protein-modified Fe(3)O(4) NPs can open up new approaches to the analytical detection of small drugs in biological liquids by SALDI-MS.
authors.affiliation: Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Osaka, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Iwaki
authors.forename: Hideya
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Arakawa
mesh_terms: D002166:Camptothecin / Q000097:blood*; D052203:Ferrosoferric Oxide / Q000737:chemistry; D006801:Humans; D007052:Ibuprofen / Q000097:blood*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008970:Molecular Weight; D010672:Phenytoin / Q000097:blood*; D012680:Sensitivity and Specificity; D012709:Serum Albumin / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014859:Warfarin / Q000097:blood* / Q000652:urine*
chemical_list: D058185:Magnetite Nanoparticles; D012709:Serum Albumin; D014859:Warfarin; D010672:Phenytoin; D007052:Ibuprofen; D052203:Ferrosoferric Oxide; D002166:Camptothecin