Surface Analysis under Ambient Conditions Using Plasma-Assisted Desorption/Ionization Mass Spectrometry Lucy V. Ratcliffe, † Frank J. M. Rutten, †,# David A. Barrett,* ,† Terry Whitmore, ‡ David Seymour, ‡ Claire Greenwood, ‡ Yolanda Aranda-Gonzalvo, ‡ Steven Robinson, § and Martin McCoustra †,⊥ Centre for Analytical Bioscience, School of Pharmacy, University of Nottingham, University Park, Nottingham, NG7 2RD, United Kingdom, Hiden Analytical Ltd., 420 Europa Boulevard, Warrington, Cheshire, WA5 7UN, United Kingdom, and Forensic Science Service, Unit 2900, Solihull Parkway, Birmingham Business Park, Birmingham, B37 7YN, United Kingdom A novel plasma-assisted desorption/ionization (PADI) method that can be coupled with atmospheric pressure sampling mass spectrometry to yield mass spectral infor- mation under ambient conditions of pressure and humid- ity from a range of surfaces without the requirement for sample preparation or additives is reported. PADI is carried out by generating a nonthermal plasma which interacts directly with the surface of the analyte. Desorp- tion and ionization then occur at the surface, and ions are sampled by the mass spectrometer. The PADI technique is demonstrated and compared with desorption electro- spray ionization (DESI) for the detection of active ingre- dients in a range of over-the-counter and prescription pharmaceutical formulations, including nonsterodial anti- inflammatory drugs (mefenamic acid, Ibugel, and ibupro- fen), analgesics (paracetamol, Anadin Extra), and Bee- cham’s “all in one” cold and flu remedy. PADI has also been successfully applied to the analysis of nicotine in tobacco and thiosulfates in garlic. PADI experiments have been performed using a prototype source interfaced with a Waters Platform LCZ single-quadrupole mass spectrom- eter with limited modifications and a Hiden Analytical HPR-60 molecular beam mass spectrometer (MBMS). The ability of PADI to rapidly detect active ingredients in pharmaceuticals without the need for prior sample prepa- ration, solvents, or exposed high voltages demonstrates the potential of the technique for high-throughput screen- ing in a pharmaceutical or forensic environment. Desorption electrospray ionization (DESI) and direct analysis in real time (DART) are two recently introduced techniques which have successfully overcome the difficulties associated with vacuum- based analyses, such as the need for vacuum compatible samples. DESI consists of directing a pneumatically assisted electrospray onto an analyte surface, coupled with collection of the desorbed ions by the MS inlet. 1 This ambient pressure ionization method has been applied to the analysis of a wide variety of compounds including peptides, 2 proteins, 2,3 pharmaceuticals, 4-6 explosives, 7,8 controlled substances, 5,9 and others. 2,10-12 DART is another atmospheric pressure ionization technique capable of rapid surface analysis. 13 DART has been applied to the detection of pharma- ceuticals, drugs of abuse, chemical warfare agents, and a multitude of other chemicals. 13 This noncontact ion source consists of a remote nonthermal plasma from which charged species are rejected with a grid system and metastable species are directed toward the surface of the analyte. 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