Nl Pis Pc

Nanoelectrospray ionization: flow rates range from a few nanoliters per minutes to a few hundred nanoliters per minutes; nanoelectrospray is performed with pulled capillaries or on chips which serve as emitter

Atmospheric pressure chemical ionization

Atmospheric pressure photoionization

Matrix assisted laser desorption ionization

Triple quadrupole: Q1 and Q3 are the mass resolving quadrupoles, q2 is the collision cell

Quadrupole ion trap: refers in general to a 3D ion trap instrument

Linear ion trap: refers in general to 2D ion trap; ion ejection is either axial or radial

Triple quadrupole linear ion trap instrument. In this instrument the quadrupole Q3 is operated either in RF/DC mode or in RF mode

Quadrupole-time of flight instrument

Tandem time of flight instrument

Fourier transform ion cyclotron resonance instrument

Multistage mass spectrometry: applies generally for ion trap mass spectrometers

Collision induced dissociation: the dissociation of ions after collisional excitation

A technique specific to reflectron time-of-flight mass spectrometers where product ions of metastable transitions or collision-induced dissociations generated in the drift tube prior to entering the reflectron are m/z separated to yield product ion spectra

Neutral loss spectrum Product ion spectrum Precursor ion spectrum Selected reaction monitoring mode

58 | 1 Mass Spectrometry in Bioanalysis - Methods, Principles and Instrumentation 1.8

Common Definitions and Abbreviations

The intention of this section is to provide to the reader a rapid and comprehensive reference for the most common definitions and acronyms used in mass spectrometry. Currently IUPAC has initiated a project to update and extend the definitions of terms related to the field of mass spectrometry. The definitions presented here (Table 1.6) are from the third draft document [16]. For more details and the latest updates, please consult


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44 Cohen, L. H.; Gusev, A. I.: Small molecule analysis by MALDI mass spectrometry. Anal. Bioanal.Chem. 2002, 373, 571-586.

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55 Schwartz, J. C.; Wade, A. P.; Enke, C. G.; Cooks, R. G.: Systematic delineation of scan modes in multidimensional mass spectrometry. Anal. Chem. 1990, 62, 1809-1818.

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Part II

Studying target-ligand interactions analyzing the ligand by MS

Drug Screening Using Gel Permeation Chromatography Spin Columns Coupled with ESI-MS

Marshall M. Siegel 2.1


2.1.1 Preface

The pharmaceutical industry has invested heavily in high throughput screening (HTS) technologies to find potential drug candidates present in large compound libraries that interact with a biological system of a potential therapeutic interest. Very often these screening techniques mimic the cellular function of the target protein. The HTS methods generally take considerable time to develop and are unique for each biological system of interest, but once developed they analyze single compounds in large arrays at high sensitivity, accounting for the high throughput capability of the methodology. The HTS methodology has been the technique of choice of pharmaceutical companies to initially screen corporate libraries for exploratory drug leads. Recently, however, a number of structurally based methods have been developed to screen corporate libraries based on the ability to observe non-covalent bonding between a protein of therapeutic interest and members of a compound library [1]. We will describe in this chapter the use of gel permeation chromatography (GPC) in the spin column mode with mass spectral detection as a reliable structural screening methodology that can be performed at high speed with large numbers of compounds, especially when analyzed as mixtures, requiring nearly no development time. This technology can be used as a primary screening technique as well as a secondary screening method to complement and verify results obtained with HTS methods.

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