Several commercial immobilized metal affinity chromatography sorbents were evaluated in this study for the analysis of two small peptide fragments of the amyloid beta-protein (A beta) (A beta(1-15) and A beta (10-20) peptides) by on-line immobilized metal affinity SPE-CE (IMA-SPE-CE). The performance of a nickel metal ion (Ni(II)) sorbent based on nitrilotriacetic acid as a chelating agent was significantly better than two coppermetal ion (Cu(II)) sorbents based on iminodiacetic acid. A BGE of 25mMphosphate (pH 7.4) and an eluent of 50mM imidazole (in BGE) yielded a 25-fold and 5-fold decrease in the LODs by IMA-SPE-CE-UV for A beta (1-15) and A beta(10-20) peptides (0.1 and 0.5 mu g/mL, respectively) with regard to CE-UV (2.5 mu g/mL for both peptides). The phosphate BGE was also used in IMA-SPE-CEMS, but the eluent needed to be substituted by a 0.5% HAc v/v solution. Under optimum preconcentration and detection conditions, reproducibility of peak areas and migration times was acceptable (23.2 and 12.0% RSD, respectively). The method was more sensitive for A beta (10-20) peptide, which could be detected until 0.25 mu g/mL. Linearity for A beta (10-20) peptide was good in a narrow concentration range (0.25-2.5 mu g/mL, R-2 = 0.93). Lastly, the potential of the optimized Ni(II)-IMA-SPE-CE-MS method for the analysis of amyloid peptides in biological fluids was evaluated by analyzing spiked plasma and serum samples.