To determine sub-ppb levels of drugs in biological samples, selective, sensitive and rapid analytical techniques are required. This work shows the possibilities for high-throughput analysis of solid-phase microextraction (SPME) directly coupled to an ion-trap mass spectrometer equipped with an atmospheric pressure chemical ionisation source. As no chromatographic separation is performed, the SPME procedure is the time-limiting step. Direct immersion SPME under non-equilibrium conditions permits the determination of lidocaine in urine within 10 min. After a 5 min sorption time with a 100 microm polydimethylsiloxane-coated fibre, the extraction yield of lidocaine from urine is about 7%. When applying 4 min desorption, using a mixture of ammonium acetate buffer (pH 4.5) and acetonitrile (85 + 15 v/v), about 10% of the analyte is retained on the fibre. An extra cleaning step of the fibre is therefore used to prevent carry-over. By use of tandem MS, no matrix interference is observed. The detection limit for lidocaine is about 0.4 ng ml(-1) and the intraday and interday reproducibility are within 14% over a concentration range of 2-45 ng ml(1).

Ultra-rapid non-equilibrium solid-phase microextraction at elevated temperatures and direct coupling to mass spectrometry for the analysis of lidocaine in urine Solid-phase microextraction (SPME) has been directly coupled to an ion-trap mass spectrometer (MS) for the determination of the model compound lidocaine in urine, hereby applying MS/MS [fragmentation of [M + H] + (m/z 235) to a fragment with m/z 86]. The throughput of samples has been increased using non-equilibrium SPME with polydimethylsiloxane (PDMS) fibers. The effect of temperature on the sorption and the desorption was studied. Elevated temperatures during sorption (658C) and desorption (558C) had a considerable influence on the speed of the extraction. The desorption was carried out with a home-made desorption chamber allowing thermostating. Only 1 min sorption and 1 min desorption were performed, after which MS detection took place, resulting in a total analysis time of 3 min. Detection limits below 1 ng/ mL could be obtained despite yields of only 2.1 and 1.5% for a 100-and a 30-lm PDMS-coated fiber, respectively. Furthermore, the determination of lidocaine in urine had acceptable reproducibilities, i.e., relative standard deviations (RSDs) below 10%. A limit of quantitation (RSD a 15%) of about 1 ng/mL was obtained. No extra wash step of the extraction fiber was required after desorption if a 30-lm coating was used, whereas not all the analyte was desorbed from the 100-lm coating in a single desorption. Therefore, the SPME-MS/MS system with a 30-lm PDMS-coated fiber for rapid non-equilibrium SPME at elevated temperatures has interesting potential for highthroughput analysis of biological samples.

High-throughput analysis of biological samples is becoming increasingly important. On-line sample pretreatment and separation increases the speed and reliability of the analysis. In order to increase the speed even more, solid-phase extraction (SPE) and solid-phase microextraction (SPME) have been directly coupled to an ion-trap mass spectrometer (ITMS). As a result, analysis times can be reduced to a few minutes.If SPE is directly coupled to the ITMS it is very important to obtain clean extracts to prevent detection problems, e.g. ion suppression. With a non-selective stationary phase, the removal of interfering matrix compounds requires an efficient washing step in which no elution of the analyte occurs. The choice of single MS vs. multiple-stage MS is also dependent on this step. Special attention has been paid to differences in chromatograms of blank samples and to ion-suppression effects. Extended AbstractMultiple-stage MS is very interesting for a reduction of matrix effects, and so a considerable increase of selectivity and sensitivity was obtained. Multiple-stage MS cannot eliminate ion suppression. SPE-MS methods with atmospheric pressure chemical ionisation (APCI) have been developed for the determination of clenbuterol in urine [1] and prednisolone in serum using a polydivinylbenzene (PDVB) and C18 stationary phase, respectively.A PDVB cartridge (10 • 2mm i. d.) allowed effective washing of the SPE phase, i.e. 50% (v/v) methanol could be used without elution of clenbuterol from the cartridge. This resulted in relatively clean extracts. Elution was performed with a flow-rate of 1.0mLmin 1 using a methanol gradient (50 to 70% in 2.5 min). However, for sensitive analysis MS-MS had to be applied. Consequently, a detection limit (LOD) of about0.5 ngmL 1 was observed for clenbuterol in urine. Despite the washing procedure severe ion suppression (45%) was observed for low levels of clenbuterol (0.5 10ngmL 1), whereas the ion suppression was less prominent for higher concentrations of clenbuterol (suppression about 4%). Even though the suppression was concentration dependent, good linearity was observed (R>0.99, range 1.0 250ngmL 1). The total analysis time was about 8.5 min, which is still relatively long due to rather low flow-rates that were applied during the different SPE steps.Prednisolone was extracted from serum by a C18 stationary phase (10 • 2 mm i.d.). Due to the apolar ring structure of the analyte it was possible to wash the stationary phase with 25% (v/v) methanol. Elution was performed using a methanol gradient (25 to 50% in 1.5 min with a 1-mL min 1 flow-rate). Subsequently, MS-MS was used for the analyis. The total set-up resulted in an LOD of 10 ng mL 1 of prednisolone in serum (Figure 1). The relatively high LOD is due to MS fragmentation of prednisolone. The total analysis time including sample pretreatment is about 5 min. No ion suppression was observed during the determination of prednisolone. Good linearity (R > 0.99) was observed over the range 10 250 ngmL 1.A first attempt to couple SP...