Mass Spectrometry for Drug Discovery and Drug Development (Korfmacher/Mass Spectrometry for Drug Discovery and Drug Development) || Index

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    Abscesses, examined by IMS, 291Absolute chemical structure, in-depth

    knowledge of, 246Absolute metabolite quantitation kit, 393Absolute quantitation, from tissue samples,

    233234Absorption assays, 98Absorption, distribution, metabolism, and

    excretion (ADME) assays. See also ADME entries; In vitro ADME entries

    frequently performed, 9798mass spectrometry for in vitro, 97113

    Absorption, distribution, metabolism, and excretion (ADME) parameters, therapeutic siRNAs and, 372

    Absorption/distribution/metabolism/excretion/toxicity (ADMET) assays, 304

    Absorption, metabolism, and excretion (AME) studies, 131

    Accelerator mass spectrometry (AMS), 2, 2728

    Acetonitrileeffect of, 69in sample extraction, 133134, 135

    Acetonitrile methanol elution, 6365Acetonitrile precipitation, 81

    Mass Spectrometry for Drug Discovery and Drug Development, First Edition. Edited by Walter A. Korfmacher. 2013 John Wiley & Sons, Inc. Published 2013 by John Wiley & Sons, Inc.

    Acid hydrolysis, MALDI-MS and, 369Acidic matrices, 368Active drug compounds, assessing

    homogeneity of, 324325Active pharmaceutical ingredients (APIs),

    249impurities in, 191

    Acylglucuronides, 56, 73, 74, 133Adduct ions, 3Adenosine triphosphate (ATP), depletion

    of, 318ADME program, for drug registration, 129.

    See also Absorption, distribution, metabolism, and excretion (ADME) entries

    ADME properties, of siRNAs, 364ADME studies, 117, 129, in animals, 132ADME support, 102Adverse drug reactions (ADRs), 339340AEE788 vascular endothelial growth factor

    receptor inhibitor, 318320Affinity selectionMS (ALIS) method, 261,

    262Agilent, 106Albumin depletion method, 178179Alkali ion exchange, with ammonium ions,


  • 428 INDEx

    Alternative fragmentation process, 28Alternative ionization methods, 28Alzheimers biomarkers, 42Ambient desorption techniques, 711Ambient ionization mass spectrometry, 7Ambient sampling/ionization techniques,

    109Ambient surface profiling, LESA for,

    221238Amine adducted ions, in PEGylated protein

    analysis, 167Ammonium hydroxide (NH4OH), 412Ammonium ions, alkali ion exchange with,

    368AMS system, components of, 28. See also

    Accelerator mass spectrometry (AMS)Amyloid peptides, HPLC-MS/MS

    quantification of, 413-Amyloid peptides, 408410Analog-to-digital converter (ADC), 344Analyte expression, 60Analyte extractionLESA in, 231232organic solvents for, 6768using LLE, 6667

    Analytesanalysis of, 34, 8annotation of, 395, 396capturing quantitative information on, 394

    chromatographically separating from phospholipids, 65

    ionization efficiency of, 225post-acquisition extraction of accurate masses of, 107

    Analyte stabilization, chemical agents in, 57

    Analytical approaches, fingerprinting techniques and, 391392

    Analytical data acquisition, in metabolomics, 390

    Analytical fingerprints, 391Analytical instrumentation, creation of, 49Analytical/wet chemistry techniques, 142Anatomy, intact protein analysis of,

    284288AnimalsADME studies in, 132metabolic profiles in, 130

    Animal studiesAUC pooling method in, 136incurred sample from, 81

    Anion exchange, 367Annotationof analytes, 395, 396in nontargeted metabolomics, 395, 396

    Antibacterial compounds, cannibalistic factors as, 291

    Antibiotic-resistant bacteria strains, 291Antibody fragmentation, 208Anticoagulants, 57Antidrug antibody purification method,

    178179Antioxidants, 133Antisense oligonucleotide therapeutic

    discovery, 372APCI HPLC-MS applications, 6. See also

    Atmospheric pressure chemical ionization (APCI); High-performance liquid chromatographymass spectrometry (HPLC-MS)

    APCI ionization mechanism, 6APCI-MS, 6. See also Mass spectrometry

    entriesAPI sources, introduction of samples into,

    108. See also Atmospheric pressure ionization (API)

    API techniques, 28AQ4N prodrug, 318Aqueous mobile phase, phase collapse and,

    7576Area under the curve (AUC), 135, 136Artificial deamidation, minimizing, 212Artificial degradation, in peptide mapping,

    211213Asn deamidation/isomerization scheme,

    205. See also Asparagine (Asn) residues

    Asparagine (Asn) residues, deamidation of, 167, 177, 204

    Aspartate (Asp)isoAsp residues from, 206isomerization of, 177

    Aspartate products, isoaspartate vs., 177Astemizole, MALDI imaging results for,

    316, 317Atmospheric pressure chemical ionization

    (APCI), 1, 56, 109, 240, 241, 245Atmospheric pressure IEM, 5. See also Ion

    evaporation model (IEM)Atmospheric pressure ionization (API), 1sources of, 39

    Atmospheric pressure ionization methods/techniques, 8, 240

  • INDEx 429

    Atmospheric pressure ion source geometries, 2

    Atmospheric pressure MALDI (API-MALDI), 13. See also Matrix-assisted laser desorption/ionization (MALDI)

    Atmospheric pressure photoionization (APPI), 1, 5, 67, 240, 241, 250

    Atmospheric pressure solid probe analysis (ASAP), 9

    AUC plasma pooling, volume calculation for, 135

    AUC pooling method, in animal studies, 136

    Automated anion-exchange purification/desalting HPLC system, 367

    Automated component detection, 121Automated compound purification systems,

    243Automated infusion, 108Automated optimization workflows, 404Automated tryptic digestion, 156Automatic analyte extraction, LESA in,

    231232Automatic gain control (AGC) procedure,

    17Automaton, 100Autoradiography, 221222. See also Whole

    body autoradiography (WBA)MALDI imaging as a complement to, 323

    Autoradiography imaging, 304, 305. See also Quantitative whole-body autoradiography entries

    Autosampling, fraction-collecting, 367368Avion TriVersa-NanoMate robotic ion

    source, 222, 223Axial ejection, radial ejection vs., 19

    Background subtraction (BgS), 48, 47, 48with noise reduction algorithm, 348350real-time dynamic, 123

    Bacteria, antibiotic-resistant strains of, 291Bacterial colonies, study of, 290291Bacterial infection, IMS applied to, 290292Best quantification strategy, 408-amyloid peptides, 408410-RAM flow scintillation analyzer (FSA),

    136, 137BgS-NoRA, 348350. See also Background

    subtraction (BgS)Bile metabolic profiling, 49Bioactivation, 352

    Bioactivation potential, of drug candidates, 340

    Bioanalysis, with full scan acquisition, 105106

    Bioanalytical (BA) applications, 240Bioanalytical mass spectrometry (MS),

    99100Bioanalytical methods, 55for target quantitation, 78

    Biochemical changes, 4142Biological drugsdefined, 149MS analysis of, 149190qualitative/quantitative analysis of, xii

    Biological fluids, tracking siRNAs in, 360Biological matrices. See also Biomatricesanalysis of siRNA from, 372376endogenous components in, 127extracting siRNAs from, 365366

    Biological properties, assessment of, 248259

    Biological sample analysis, HRMS for, 414415

    Biological samplescollection, storage, and preparation of, 5659

    drug-derived material in, 133ensuring stability of, 133pooling of, 135136

    Biologic pharmaceuticals, characteristics of, 201. See also Biologics drugs

    Biologicscharacterization of, 191chemical degradations in, 210degradation characterization in, 201211future developments in imaging, 326impurities and degradation products in small-molecule, 191220

    MALDI-MS technique and, 192Biologics drugs, U.S. market for, 201202Biomarker concentration measurements, 42Biomarker measurement assays, targeted

    metabolomic analyses vs., 393394Biomarker research, 42Biomarkers, 4142in disease assessment, 403interest in, 289

    Biomatrices, isolation of siRNAs from, 364. See also Biological matrices

    Biomedical field, AMS in, 28Biotransformation analysis, of radioactive

    samples, 136, 137

  • 430 INDEx

    Biotransformation studies, samples for, 132133

    Blood samples, 118119Boronphenylalanine (BPA)-mediated boron

    neutron capture therapy, 307Bottom-up methods, 192Brain regions, IMS in redefining, 286287Breast cancer, IMS and, 289Breast cancer tissues, imaging, 290Bromine, in trapping agents, 341n-Butyl chloride, 67, 68

    C16:0 lyso-PC, extraction of, 68Cancer biology, IMS studies of, 288290. See

    also Breast cancer entries; Oncology drugs; Tumor entries

    Cancer tissue microarrays, analyzing after in situ digestion, 293. See also Pancreatic cancer tissue microarray

    Cancilla, Mark T., ix, 357Cannibalistic factors, as antibacterial

    compounds, 291Capillary columns, monolithic, 367Capillary electrophoresis (CE), 391, 394Caprioli, Richard M., ix, 277, 327, 328CaptiveSpray ion source, 4849Carboxylic acid metabolite, 74Cassette analysis, 104Cassette incubation, 104Cassette incubation/HRAM analysis

    approach, 106. See also High-resolution accurate mass (HRAM) systems

    Cation exchange (CEx), in desalting samples, 365. See also CEx fractionation

    Cation exchange chromatography, 155Cations, effects of small, 60Centroid data, 79Centroiding methodology, 419Centroid mode, MEWS applied in, 420Cetrorelix, 410CEx fractionation, 169. See also Cation

    exchange (CEx)Chalcone synthetase gene, suppression of,

    357Charge residue, 5Charge residue model (CRM), 4, 5Charge state reduction methods, in

    PEGYLATED protein analysis, 167Charge states, CID behavior of, 369370,

    371Chelating agents, 365

    Chemical agents, in analyte stabilization, 57Chemical biomarkers, 42Chemical degradants, detection of, 210Chemical degradation, 204210Chemical derivatizationapplications of, 140141for structural elucidation, 140141

    Chemical derivatization experiments, 192Chemically modified oligonucleotidesfragmentation of, 370sequencing program for, 378

    Chemically reactive metabolites, 339Chem