Liquid chromatography-tandem mass spectrometry, employing electrospray ionization (ESI), has been applied in the analysis of many drugs and drug metabolites. Sample preparation has been an important part of this technique when analyzing biological samples. Here we describe a high-volume urine screening technique for approximately 40 different drugs of abuse as well as methods for quantification of many other drugs in serum, plasma, and whole blood. These techniques can be used in many different settings from clinical and forensic toxicology examinations to pharmacokinetic studies. Sample preparation procedures range from simple "dilute and shoot" methods to more extensive solid-phase extraction techniques.
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