title: A general analytical platform and strategy in search for illegal drugs.
abstract: An effective screening procedure to identify and quantify active pharmaceutical substances in suspected illegal medicinal products is described. The analytical platform, consisting of accurate mass determination with liquid chromatography time-of-flight mass spectrometry (LC-QTOF-MS) in combination with nuclear magnetic resonance (NMR) spectroscopy provides an excellent analytical tool to screen for unknowns in medicinal products, food supplements and herbal formulations. This analytical approach has been successfully applied to analyze thousands of samples. The general screening method usually starts with a methanol extraction of tablets/capsules followed by liquid chromatographic separation on a Halo Phenyl-Hexyl column (2.7μm; 100mm×2.1mm) using an acetonitrile/0.1% formic acid gradient as eluent. The accurate mass of peaks of interest was recorded and a search made against an in-house database containing approximately 4200 substances, mostly pharmaceutical compounds. The search could be general or tailored against different classes of compounds. Hits were confirmed by analyzing a reference substance and/or by NMR. Quantification was normally performed with quantitative NMR (qNMR) spectroscopy. Applications for weight-loss substances like sibutramine and orlistat, sexual potency enhancement (PDE-5 inhibitors), and analgesic drugs are presented in this study. We have also identified prostaglandin analogues in eyelash growth serum, exemplified by isopropyl cloprostenate and bimatoprost. For creams and ointments, matrix solid-phase dispersion (MSPD) was found to give a clean extracts with high recovery prior to LC-MS analyses. The structural elucidation of cetilistat, a new weight-loss substance recently found in illegal medicines purchased over the Internet, is also presented.
authors.affiliation: Medical Products Agency, P.O. Box 26, SE-751 03 Uppsala, Sweden; Division of Analytical Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, SE-751 23 Uppsala, Sweden. Electronic address: imjo@telia.com.
authors.forename: Monika
authors.initials: M
authors.lastname: Johansson
authors.affiliation: Medical Products Agency, P.O. Box 26, SE-751 03 Uppsala, Sweden.
authors.forename: Dick
authors.initials: D
authors.lastname: Fransson
authors.affiliation: Medical Products Agency, P.O. Box 26, SE-751 03 Uppsala, Sweden.
authors.forename: Torgny
authors.initials: T
authors.lastname: Rundlöf
authors.affiliation: Medical Products Agency, P.O. Box 26, SE-751 03 Uppsala, Sweden. Electronic address: Ngoc-Hang.Huynh@mpa.se.
authors.forename: Ngoc-Hang
authors.initials: NH
authors.lastname: Huynh
authors.affiliation: Medical Products Agency, P.O. Box 26, SE-751 03 Uppsala, Sweden; Division of Analytical Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, SE-751 23 Uppsala, Sweden.
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Arvidsson
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D058110:Counterfeit Drugs / Q000032:analysis*; D062313:Databases, Pharmaceutical; D004304:Dosage Forms; D009682:Magnetic Resonance Spectroscopy / Q000379:methods* / Q000592:standards; D000432:Methanol / Q000737:chemistry; D015394:Molecular Structure; D008970:Molecular Weight; D011786:Quality Control; D015203:Reproducibility of Results; D012997:Solvents / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods* / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards
chemical_list: D058110:Counterfeit Drugs; D004304:Dosage Forms; D012997:Solvents; D000432:Methanol
keywords: Accurate mass determination; LC–QTOF-MS; Quantitative NMR (qNMR); Screening; Suspected illegal medicines