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A unique site-directed, i.e.in-pore and on-column derivatization method was developed for direct and fully automated analysis of aldehydes in human plasma by combining SPE (Solid Phase Extraction) with HPLC-UV.A Restricted Access Material (RAM; LiChrospher ADS C4 (Merck) was selected as SPE-column packing for on-line sample clean-up and site-directed derivatization.High-molecular-weight interfering constituents of sample matrix (e.g.proteins) are eliminated based on size-exclusion chromatography, while low-molecular-weight target analytes (hexanal and heptanal) have free access to the internal pore surface.These properties allow a site-directed, i.e.in-pore derivatization of the extracted analytes.