The use of turbulent flow chromatography (TFC) as a method for the rapid metabonomic LC-MS analysis of plasma as an alternative to solvent-based protein precipitation has been investigated. This comparison has shown that TFC can be effectively used in this application with the benefit that off-line sample handling is significantly reduced. However, analysis of the data obtained via TFC for human plasma reveals substantial differences in the overall metabolite profiles compared with methanol-precipitated HPLC-MS. This seems in part at least to be related to greatly reduced amounts of phospholipids (ca. 10 fold reduction) for the turbulent flow methodology compared with protein-precipitated samples. The significance of these differences with respect to metabolite profiles as a result of the sample preparation method used are discussed.