Simultaneous determination of fentanyl and midazolam in plasma using direct solid-phase microextraction before gas chromatography-mass spectrometry analysis

We developed a rapid, specific, and sensitive solid-phase extraction method followed by gas chromatography-mass spectrometry analysis for the determination of fentanyl, midazolam or both drugs simultaneously in plasma samples. Various solid-phase microextraction fibres, extraction and desorption conditions were tested in the search of the best linearity, sensitivity and clean-up. The optimal solid-phase microextraction conditions were obtained with a new 65-mum polydimethylsiloxane/divinylbenzene (PDMS/DVB) fibre. Because of the high extraction selectivity and efficiency, the quantification limit for fentanyl and midazolam could be down to 0.8 ng mL(-1) and I ng mL(-1), respectively, for a plasma volume of 1 mL. The method described is sensitive enough for analysed fentanyl and midazolam in plasma samples for toxicological screening and therapeutic drug monitoring.