Analytica Chimica Acta 556 (2006) 104–111 Separation of antidepressants by capillary electrophoresis with in-line solid-phase extraction using a novel monolithic adsorbent David Schaller, Emily F. Hilder ∗ , Paul R. Haddad Australian Centre for Research on Separation Science (ACROSS), School of Chemistry, University of Tasmania, Private Bag 75, Hobart 7001, Tasmania, Australia Received 9 April 2005; received in revised form 19 July 2005; accepted 21 July 2005 Available online 22 August 2005 Abstract The separation of three selective serotonin reuptake inhibitors (SSRIs) by capillary electrophoresis (CE) with fully integrated solid-phase extraction (SPE) is described. Polymeric monolithic SPE modules were prepared in situ within a fused silica capillary from either butyl methacrylate-co-ethylene dimethacrylate or 3-sulfopropyl methacrylate-co-butyl methacrylate-co-ethylene dimethacrylate. Using a 1 cm SPE module placed at the inlet of the capillary, a mixture of sertraline, fluoxetine and fluvoxamine was extracted from aqueous solution by applying a simple pressure rinse. Under pressure-driven conditions, efficient elution was possible from both SPE materials investigated using 50mM phosphate buffer, pH 3.5 in acetonitrile (20/80, v/v). Two different strategies were investigated for the efficient elution and subsequent CE separation. Injection of an aqueous sample plug directly into the non-aqueous elution/separation buffer was found to be unsuitable with poor elution profiles observed in the electrodriven mode. Alternatively, a sample plug equivalent to several capillary volumes could be injected by pressure followed by filling the capillary with the non-aqueous elution/separation buffer from the outlet end using a combination of pressure and electrodriven flow. Using a neutral monolith, efficient elution/separation was not possible due to an unstable electroosmotic flow (EOF), however, by adding the ionisable monomer, 3-sulfopropyl methacrylate to the SPE module to increase and stabilise the EOF, it was possible to achieve efficient elution from the SPE module, followed by baseline separation by CE using a 200 mM acetate buffer, pH 3.5 in acetonitrile (10/90, v/v). With enrichment factors of over 500 achieved for each of the analytes this demonstrates the potential of in-line SPE-CE for the sensitive analysis of these drugs. © 2005 Elsevier B.V. All rights reserved. Keywords: Polymer monolith; In-line solid-phase extraction; Capillary electrophoresis; Drug analysis 1. Introduction The determination of small molecules such as drugs and metabolites in biological fluids (e.g. urine, plasma or serum) is essential for compiling information in biomedical, pharma- cological or forensic studies as well as drug testing of elite athletes. More recently, in the “post-genomic” era, metabolic profiling is also becoming increasingly more important as ∗ Corresponding author. Tel.: +61 3 6226 7670; fax: +61 3 6226 2858. E-mail address: Emily.Hilder@utas.edu.au (E.F. Hilder). a means to provide information on disease states, toxic- ity and gene function [1]. Capillary electrophoresis (CE) offers several advantages over chromatographic techniques for the determination of small molecules in biological flu- ids, especially when only small amounts of sample are available. The main advantages of CE over other methods include the higher separation efficiency, unique separation selectivity, smaller sample volume required and the lower costs due to low solvent consumption and relatively inex- pensive capillaries compared to chromatographic columns. Despite these advantages, the routine application is lim- ited due to several problems that still must be solved. First 0003-2670/$ – see front matter © 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.aca.2005.07.035