Potentiometric detection in UPLC as an easy alternative to determine cocaine in biological samples Devin Daems a,b , Alexander L. N. van Nuijs c , Adrian Covaci c , Ezat Hamidi-Asl a , Guy Van Camp b and Luc J. Nagels a * ABSTRACT: The analytical methods which are often used for the determination of cocaine in complex biological matrices are a prescreening immunoassay and confirmation by chromatography combined with mass spectrometry. We suggest an ultra- high-pressure liquid chromatography combined with a potentiometric detector, as a fast and practical method to detect and quantify cocaine in biological samples. An adsorption/desorption model was used to investigate the usefulness of the potentiometric detector to determine cocaine in complex matrices. Detection limits of 6.3 ng mL À1 were obtained in plasma and urine, which is below the maximum residue limit (MRL) of 25 ng mL À1 . A set of seven plasma samples and 10 urine sam- ples were classified identically by both methods as exceeding the MRL or being inferior to it. The results obtained with the UPLC/potentiometric detection method were compared with the results obtained with the UPLC/MS method for samples spiked with varying cocaine concentrations. The intraclass correlation coefficient was 0.997 for serum (n=7) and 0.977 for urine (n=8). As liquid chromatography is an established technique, and as potentiometry is very simple and cost-effective in terms of equipment, we believe that this method is potentially easy, inexpensive, fast and reliable. Copyright © 2014 John Wiley & Sons, Ltd. Keywords: cocaine; UPLC; potentiometry; plasma; urine Introduction Chromatographic determination of organic substances in com- plex biological samples is still a major problem. These matrices are known to contain thousands of components in a log–normal concentration distribution (Enke and Nagels, 2011). The peak ca- pacity of high-performance liquid chromatography (HPLC) and ultra-high-performance liquid chromatography (UPLC) systems is much too low to separate even a fraction of the compounds present (Davis, 2012). The successful coupling of these separa- tion methods to mass spectrometry improved the resolving power of chromatographic methods for the determination of secondary metabolites dramatically (Forcisi et al., 2013). Yet, the chromatography mass spectrometry systems are too com- plex and expensive to screen large numbers of samples, and prescreening techniques such as enzyme-linked immunosor- bent assay are usually used. The latter technique, however, is prone to interference, is limited to a small set of compounds and gives only qualitative information. On the other hand, the coupling of chromatographic methods to a simple, selective and sensitive detector can also give a solution either for the prescreening, or for the determination of single or multiple compounds in complex mixtures. Potentiometric sensors have potential in this respect. They are currently not used in combina- tion with chromatographic methods, although they were con- sidered for this purpose decades ago (Alexander et al., 1981; Haddad et al., 1984). Our group demonstrated that it was possi- ble to use a potentiometric sensor in HPLC determinations of organic acids and basic drugs (Bazylak and Nagels, 2003; Nagels et al., 2007; Zielinska et al., 2004), and more recently, in the UPLC determination of alkaloids (Daems et al., 2013). The sensor was also used in capillary electrophoresis determination of drugs of abuse (Sekula et al., 2006). The sensor can handle the detection of organic ionizable substances, and is nonresponsive to neutral substances. At present, the selectivity of potentiometric sensors is limited as far as ionic organic compounds are concerned, and its selectivity is governed by lipophilicity (Vissers et al., 2009). The interaction of the analyte with the sensor surface is a deci- sive factor, and we showed recently that it can be determined with binding kinetics analysis (De Wael et al., 2012). Cocaine and its metabolites, benzoylecgonine and ecgonine methyl ester are the major indicators of cocaine use in blood and urine samples (Cardona et al., 2006; Huestis et al., 2007). Cocaine itself is a good marker for recent cocaine use during * Correspondence to: L. J. Nagels, University of Antwerp, Department of Chemistry, Groenenborgerlaan 171, B-2020 Antwerp, Belgium. Email: luc. nagels@uantwerpen.be a University of Antwerp, Department of Chemistry, Groenenborgerlaan 171, B-2020, Antwerp, Belgium b University of Antwerp, Centre of Medical Genetics, Universiteitsplein 1, B-2610, Antwerp, Belgium c University of Antwerp, Toxicological Center, Universiteitsplein 1, B-2610, Antwerp, Belgium Abbrevations used: FIA, flow injection analysis; ICC, intraclass correlation coefficient; MRL, maximum residue limit; NPOE, 2-nitrophenyloctylether; TCPB, tetra(p-chlorophenyl)borate. Biomed. Chromatogr. 2014 Copyright © 2014 John Wiley & Sons, Ltd. Research article Received: 22 August 2014, Revised: 2 October 2014, Accepted: 27 October 2014 Published online in Wiley Online Library (wileyonlinelibrary.com) DOI 10.1002/bmc.3400