Abstract
New Psychoactive Substances (NPS), also known as design drugs, are
developed by modification of the chemical structure of the initially prohibited
substances. The idea behind this strategy is to create alternatives for consumption and
to evade national and international control measures applied to controlled substances,
bypassing the legislative prohibition. In this context, the emergence of NPS has raised
questions about the analytical methods that can be applied to identify and to
characterize these substances in different scenarios, including biological fluids
(serum/plasma, whole blood, oral fluid, and urine). Because biological fluids are
complex matrixes, a sample preparation step is required to remove undesired
endogenous matrix components and to isolate and pre-concentrate the analytes before
chromatographic analysis. Different extraction or sample preparation techniques such
as liquid-liquid extraction, solid phase extraction, dispersive liquid-liquid
microextraction, and microextraction by packed sorbent can be used prior to
chromatographic analysis (gas chromatography, mass spectrometry, or liquid
chromatography mass spectrometry). All these techniques involve many factors that
must be optimized so that the analytical method can detect NPS in biological samples.
Tools like design of experiments (DoE) and Response Surface Methodology (RSM)
can contribute to the study and optimization of the variables involved in these
analytical techniques. This book chapter shows how experimental design tools (full
factorial design, fractional factorial design, Plackett-Burman design, Box-Behnken
design, central composite design) and response surface methodology can aid the
development of analytical methods for the analysis of drugs of abuse in biological
fluids.