Rapid screening of drug compounds in urine using a combination of microextraction by packed sorbent and rotating micropillar array electrospray ionization mass spectrometry Katrine Nielsen 1 , Frants R. Lauritsen 2 , Teemu Nissilä 3,4 and Raimo A. Ketola 3 * 1 Department of Chemistry, University of Copenhagen, Denmark 2 Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Denmark 3 Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, Finland 4 Division of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Helsinki, Finland RATIONALE: Screening of drugs from urine samples can be non-selective or laborous, using either immunological, gas chromatography/mass spectrometry (GC/MS) or liquid chromatography (LC)/MS methods. Therefore, a rapid screening method for selected drugs in urine sample was developed in a proof-of-principle manner, utilizing simple and fast techniques for both sample treatment and sample analysis. METHODS: Sample treament of spiked urine samples was performed with microextraction by packed sorbent (MEPS). Five different sorbent materials (C 2 ,C 8 ,C 18 , M1 (cation exchanger), and Sil (pure silica)) were tested for the MEPS. The sample analysis was performed using a circular microchip with 60 micropillar electrospray ionization (mPESI) tips com- bined with a mass spectrometer (either a triple-quadrupole or ion-trap mass spectrometer) without any chromatographic step. RESULTS: The sample treatment/analysis setup was tested using three drug compounds at a concentration of 1 mM. We found that the C 2 ,C 8 and C 18 sorbents in combination with 96% alkaline methanol as an eluent worked the best. All compounds were easily detected and identified by MS/MS in spiked urine samples. The whole qualitative analytical procedure was rapid as the sample treatment together with the MS analysis took about 5 min per sample. CONCLUSIONS: A rapid screening method for selected drugs from urine samples was developed, providing adequate selectivity and sensitivity, as well as a short total analysis cycle time. This new method can provide a new alternative for screening purposes, as both the extraction and analysis steps could be totally automatized. Copyright © 2011 John Wiley & Sons, Ltd. Microextraction by packed sorbent (MEPS, also called micro- extraction in packed syringe) is a new format for solid-phase extraction (SPE) that has been miniaturized to work with sample volumes as small as 10 mL as recently reviewed. [1] The MEPS sorbent bed is integrated into a liquid handling syringe that allows for low void volume sample manipula- tions either manually or in combination with laboratory robotics. [2] In MEPS approximately 1 mg of the solid packing material is packed inside a syringe (100–250 mL) as a plug or between the barrel and the needle as a cartridge. The com- mercially available MEPS syringes use the same sorbents as conventional SPE columns. The key aspect of MEPS is that the solvent volume used for the elution of the analytes is of a suitable order of magnitude to be injected directly into gas chromatography (GC) or liquid chromatography (LC) sys- tems. This new technique is fast, simple and it requires very small volumes of samples to produce comparable results to a conventional SPE technique. Another major advantage of the MEPS syringes is their re-usability as plasma and urine samples can be extracted more than 100 times using the same syringe. [1] So far MEPS has been applied in clinical and pre-clinical studies for quantification of drugs and metabolites in blood, plasma, and urine. For example, several drugs such as 4-OH- 2,6-xylidine and its conjugates, [3] ropivacaine, [4] b-blockers acebutolol and metoprolol, [5] neurotransmitters dopamine and serotonine, [6] methadone, [7] fluoroquinolones, [8] cocaine and cocaine metabolites, [9] and atorvastatin and its metabolites [10] have been extracted from urine samples using the MEPS technique. In most cases the MEPS extraction has been com- bined with either gas chromatography/mass spectrometry (GC/MS) or liquid chromatography/tandem mass spectrometry (LC/MS/MS), but also capillary electrophoresis (CE)/MS [8] and direct analysis in real time time-of-flight (DART-TOF) [9] instruments have been employed in the analysis. In quantita- tive work the calibration ranges were varied between 1 and 2000 nM. The sample volumes used in extractions were only 30–100 mL, making the sample treatment cost-effective and rapid. In addition, several sorbent materials, such as C 2 ,C 8 , C 18 , ENV, MCX, SCX, and polystyrene, have been tested in extraction, but any universal choice cannot be concluded as adsorption and desorption properties largely vary, depending on the chemical structure of the drug. * Correspondence to: R. A. Ketola, Centre for Drug Research, Faculty of Pharmacy, Viikinkaari 5E, FI-00014 University of Helsinki, Finland. E-mail: raimo.ketola@helsinki.fi Copyright © 2011 John Wiley & Sons, Ltd. Rapid Commun. Mass Spectrom. 2012, 26, 297–303 Research Article Received: 5 September 2011 Revised: 20 October 2011 Accepted: 20 October 2011 Published online in Wiley Online Library Rapid Commun. Mass Spectrom. 2012, 26, 297–303 (wileyonlinelibrary.com) DOI: 10.1002/rcm.5304 297