113 ISSN: 1469-0667 © IM Publications LLP 2012 doi: 10.1255/ejms.1175 All rights reserved EUROPEAN JOURNAL OF MASS SPECTROMETRY The direct analysis of mixtures by mass spectrometry (MS) has always been a challenging task. The presence of different analytes having different concentrations commonly results in the detection of the most abundant species at the expense of those present in small traces due to ion suppression effects during both the ionization and detection steps. Conversely, a mixture component may dominate the mass spectrum because of exceptionally high ionization efficiency, thus discriminating the observation of any other, possibly major, components. 1 As a dispersive device that sorts ions formed in the ion source according to their mass-to-charge ratios (m/z), the mass spectrometer can separate molecules that differ in mass; nevertheless, the resolving power and mass accuracy of the mass analyzer set a limit to the measurable mass differences, which may prevent the identification of Interfacing multistage mass spectrometry with liquid chromatography or ion mobility separation for synthetic polymer analysis Vincenzo Scionti, a,b Bryan C. Katzenmeyer, a Nilüfer Solak Erdem, a,c Xiaopeng Li a and Chrys Wesdemiotis a,* a Department of Chemistry, The University of Akron, Akron, OH 44325, USA. E-mail: wesdemiotis@uakron.edu b Current address: PPG Industries, Coating Innovation Center, Allison Park, PA 15101, USA c Current address: TÜBI · TAK Marmara Research Centre, Kocaeli, Turkey Synthetic polymers are naturally mixtures of homologs, even in pure form. More complexity is introduced by the presence of different comonomers, end groups and/or macromolecular architectures. The analysis of such systems is substantially facilitated by interfacing mass spectrometry (MS), which disperses based on mass, with an additional level of separation involving either interactive liquid chromatography (LC) or ion mobility (IM) spectrometry, both of which are readily coupled online with electrospray ionization and MS detection. IM-MS separates in the gas phase, post-ionization and, therefore, is ideally suitable for labile and reactive polymers. Its usefulness is illustrated with the characterization of non-covalent siloxane–saccharide complexes, metallosupramolecular assem- blies and an air- and moisture-sensitive inorganic polymer, poly(dichlorophosphazene). Conversely, LC-MS which separates in solution phase, before ionization, is most effective for the analysis of polymeric mixtures whose components differ in polarity. Interactive LC conditions can be optimized to disperse by the content of hydrophobic units, as is demonstrated for amphiphilic polyether copolymers and sugar-based nonionic surfactant blends. Both LC-MS and IM-MS can be extended into a third dimension by tandem mass spectro- metry (MS 2 ) studies on select oligomers, in order to obtain insight into individual end groups and isomeric architectures, comonomer sequences and degree of substitution, for example, by hydrophobic functionalities. Keywords: synthetic polymers, reverse-phase liquid chromatography, ion mobility separations, copolymers, surfactant, polymer architecture Introduction V. Scionti et al., Eur. J. Mass Spectrom. 18, 113–137 (2012) Received: 20 March 2012 ■ Accepted: 26 April 2012 ■ Publication: 8 May 2012 Dedicated to Professor Johan K. Terlouw for his inspiring and seminal work in gas-phase ion chemistry and mass spectrometry fundamentals Special Issue Honouring Hans Terlouw