When tl aces of drugs must be determined in complex matrices such as biolog
ical fluids, sample handling is usually required before chromatographic ana
lysis. The goals of sample pretreatment are to release the analyte from a c
onjugate or from proteins in the biological matrix, to eliminate proteins (
which can clog the chromatographic column) and endogenous compounds (which
can interfere in the assay i.e. sample clean-lip), and to increase the conc
entration of the analyte to reach the detection range of the detector (trac
e enrichment). This article describes the different sample clean-up techniq
ues available. In current bioanalytical methods, dialysis and solid phase e
xtraction (SPE) are increasingly used for sample preparation in place of tr
aditional methods, such as deproteinization or liquid-liquid extraction. By
using sample processors, the analysis of drugs in plasma can be fully auto
mated and directly coupled to the analytical system. This is of particular
interest when the number of samples is large. Most often, the use of an aut
omated sample handling procedure lends to better results in terms of accura
cy and precision than do manual techniques.