A simple, fast and sensitive method for the determination of quetiapine in human blood has been developed and validated. The method involved a basic liquid–liquid extraction procedure and subsequent analysis by gas chromatography–mass spectrometry, previous derivatization with bis(trimethylsilyl)-trifluoro-acetamide and chorotrimethylsilane (99 : 1). The methods of validation included linearity with a correlation coefficient > 0.99 over the range 0.02–1 µg ml–1, intra- and interday precision (always < 12%) and accuracy (mean relative error always < 12%) to meet the bioanalytical acceptance criteria. The limit of detection was 0.005 µg ml–1. The procedure was further applied to post mortems from the Institute of Legal Medicine, University of Santiago de Compostela. Copyright © 2013 John Wiley & Sons, Ltd.