Tailor-made precolumn packings for HPLC integrated extractive clean-up of (bio)fluids are characterized by possessing a defined diffusion barrier and a biocompatible outer particle surface (restricted access materials, RAM). Only analytes of low molecular mass have free access to the binding centers at the inner pore surface, and thus can be retained and extracted selectively. These adsorbents allow the easy, inexpensive installation and economic operation of fully automated coupled-column systems for repetitive on-line solid-phase extraction (SPE), and the subsequent analytical separation of untreated (bio)fluids.