Bio-sample preparation and gas chromatographic determination of benzodiazepines--a review

Benzodiazepines have become commonly prescribed medicines worldwide in the therapy of anxiety, sleep disorders and convulsive attacks because they are relatively safe, with mild side effects. The availability of rapid, sensitive and selective analytical methods is essential for the determination of these drugs in clinical and forensic cases. Benzodiazepines are usually present at trace levels (μg/mL or ng/mL) in a complex biological matrix, and the potentially interfering compounds need to be removed before analysis. Therefore, a sample preparation technique is often mandatory, both to extract the drugs of interest from the matrices and to increase their concentration. An extended and comprehensive review is presented herein, focusing on bio-sample preparation (pretreatment, extraction and derivatization) and gas chromatographic methods applied for the quantification of 1,4-benzodiazepines.