{"product_id":"targeted-biomarker-quantitation-by-lcms-9781119103066","title":"Targeted Biomarker Quantitation by LCMS","description":"\u003cb\u003eBook Synopsis\u003c\/b\u003e\u003cbr\u003e\u003cp\u003e\u003cb\u003eThe first book to offer a blueprint for overcoming the challenges to successfully quantifying biomarkers in living organisms\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003eThe demand among scientists and clinicians for targeted quantitation experiments has experienced explosive growth in recent years. While there are a few books dedicated to bioanalysis and biomarkers in general, until now there were none devoted exclusively to addressing critical issues surrounding this area of intense research. \u003ci\u003eTarget Biomarker Quantitation by LC-MS\u003c\/i\u003e provides a detailed blueprint for quantifying biomarkers in biological systems. It uses numerous real-world cases to exemplify key concepts, all of which were carefully selected and presented so as to allow the concepts they embody to be easily expanded to future applications, including new biomarker development.\u003c\/p\u003e \u003cp\u003e\u003ci\u003eTarget Biomarker Quantitation by LC-MS\u003c\/i\u003e primarily focuses on the assay establishment for biomarker quantitationa critical issue rarely treated in depth. I\u003cbr\u003e\u003cbr\u003e\u003cb\u003eTable of Contents\u003c\/b\u003e\u003cbr\u003e\u003c\/p\u003e\u003cp\u003eList of Contributors xv\u003c\/p\u003e \u003cp\u003ePreface xix\u003c\/p\u003e \u003cp\u003eAbbreviations xxiii\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart I Overview 1\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Overview of Targeted Quantitation of Biomarkers and Its Applications 3\u003cbr\u003e\u003ci\u003eNaidong Weng\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e1.1 Introduction 3\u003c\/p\u003e \u003cp\u003e1.2 Biomarker Definition 4\u003c\/p\u003e \u003cp\u003e1.3 Current Challenges of a Biomarker 5\u003c\/p\u003e \u003cp\u003e1.4 Biomarker Validation Process 6\u003c\/p\u003e \u003cp\u003e1.5 Current Regulatory Requirement for Target Biomarker Quantitation 6\u003c\/p\u003e \u003cp\u003e1.6 Challenges of Biomarker Quantitation 7\u003c\/p\u003e \u003cp\u003e1.7 Current Technologies for Biomarker Quantitation 8\u003c\/p\u003e \u003cp\u003e1.7.1 LC–MS 8\u003c\/p\u003e \u003cp\u003e1.7.2 GC–MS 8\u003c\/p\u003e \u003cp\u003e1.7.3 Ligand]Binding Assay 9\u003c\/p\u003e \u003cp\u003e1.7.4 Flow Cytometry 9\u003c\/p\u003e \u003cp\u003e1.7.5 Quantitative PCR (qPCR) 9\u003c\/p\u003e \u003cp\u003e1.8 Current Biomarker Quantitation Applications 9\u003c\/p\u003e \u003cp\u003e1.8.1 Protein Biomarkers 9\u003c\/p\u003e \u003cp\u003e1.8.2 Peptide Biomarkers 10\u003c\/p\u003e \u003cp\u003e1.8.3 RNA Biomarkers 11\u003c\/p\u003e \u003cp\u003e1.8.4 Nucleotide Biomarkers 11\u003c\/p\u003e \u003cp\u003e1.8.5 Small Molecule Biomarkers 11\u003c\/p\u003e \u003cp\u003e1.9 Conclusion and Future Perspective 12\u003c\/p\u003e \u003cp\u003eReferences 13\u003c\/p\u003e \u003cp\u003e2 Translational Application of Biomarkers 17\u003cbr\u003e\u003ci\u003eRay Bakhtiar\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e2.1 Introduction 17\u003c\/p\u003e \u003cp\u003e2.2 Translational Medicine 17\u003c\/p\u003e \u003cp\u003e2.3 Biomarkers 18\u003c\/p\u003e \u003cp\u003e2.4 Biomarker Categories 18\u003c\/p\u003e \u003cp\u003e2.5 Neurobiological Disorders 21\u003c\/p\u003e \u003cp\u003e2.6 Cardiovascular Disorders 22\u003c\/p\u003e \u003cp\u003e2.7 Chronic Obstructive Pulmonary Disease 23\u003c\/p\u003e \u003cp\u003e2.8 Oncology 24\u003c\/p\u003e \u003cp\u003e2.9 Biomarker Measurements and Regulatory Considerations 26\u003c\/p\u003e \u003cp\u003e2.10 Conclusions 27\u003c\/p\u003e \u003cp\u003eReferences 29\u003c\/p\u003e \u003cp\u003e3 Current Regulatory Guidance Pertaining Biomarker Assay Establishment and Industrial Practice of Fit]for]Purpose and Tiered Approach 35\u003cbr\u003e\u003ci\u003eNaidong Weng\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e3.1 Introduction 35\u003c\/p\u003e \u003cp\u003e3.2 Current Regulatory Guidance and Interpretation 36\u003c\/p\u003e \u003cp\u003e3.3 Current Industrial Discussion and Recommendations 37\u003c\/p\u003e \u003cp\u003e3.4 Considerations for Assay Validation and Sample Analysis 39\u003c\/p\u003e \u003cp\u003e3.4.1 Sensitivity 40\u003c\/p\u003e \u003cp\u003e3.4.2 Specificity and Selectivity 40\u003c\/p\u003e \u003cp\u003e3.4.3 Matrix Effects and Sample Variables 40\u003c\/p\u003e \u003cp\u003e3.4.3.1 Authentic Analyte\/Authentic Matrix Approach 40\u003c\/p\u003e \u003cp\u003e3.4.3.2 Surrogate Analyte\/Authentic Matrix Approach 40\u003c\/p\u003e \u003cp\u003e3.4.3.3 Authentic Analyte\/Surrogate Matrix Approach 40\u003c\/p\u003e \u003cp\u003e3.4.4 Accuracy\/Precision 40\u003c\/p\u003e \u003cp\u003e3.4.5 Stability 41\u003c\/p\u003e \u003cp\u003e3.4.6 Sample Analysis Consideration 41\u003c\/p\u003e \u003cp\u003e3.5 Examples of Fit]for]Purpose and Tiered Approach 41\u003c\/p\u003e \u003cp\u003e3.5.1 Relative Quantification of Glyco]isoforms of Intact Apolipoprotein C3 in Human Plasma by LC]HRMS 41\u003c\/p\u003e \u003cp\u003e3.5.2 Quantification of 4β]Hydroxycholesterol Endogenous Biomarker for CYP3A4 Activity in Plasma Samples 41\u003c\/p\u003e \u003cp\u003e3.5.3 Quantitation of Leukotriene B4 in Human Sputum as a Biomarker Using UPLC–MS\/MS 42\u003c\/p\u003e \u003cp\u003e3.6 Conclusion 42\u003c\/p\u003e \u003cp\u003eReferences 42\u003c\/p\u003e \u003cp\u003e4 Modern Liquid Chromatography and Mass Spectrometry for Targeted Biomarker Quantitation 45\u003cbr\u003e\u003ci\u003eWenying Jian\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e4.1 Introduction 45\u003c\/p\u003e \u003cp\u003e4.2 Liquid Chromatography 45\u003c\/p\u003e \u003cp\u003e4.2.1 Importance of Separation 45\u003c\/p\u003e \u003cp\u003e4.2.2 Basic Principle of LC 47\u003c\/p\u003e \u003cp\u003e4.2.3 Major Modes of LC Used for Targeted Biomarker Quantitation 47\u003c\/p\u003e \u003cp\u003e4.2.4 Modern LC Technologies 49\u003c\/p\u003e \u003cp\u003e4.2.4.1 HPLC and UHPLC 49\u003c\/p\u003e \u003cp\u003e4.2.4.2 Miniaturized Column LC 50\u003c\/p\u003e \u003cp\u003e4.2.4.3 2D]LC 51\u003c\/p\u003e \u003cp\u003e4.3 Mass Spectrometry 51\u003c\/p\u003e \u003cp\u003e4.3.1 Major Types of MS Used for Targeted Biomarker Quantitation 51\u003c\/p\u003e \u003cp\u003e4.3.2 Ionization Techniques 54\u003c\/p\u003e \u003cp\u003e4.3.3 Ion Mobility 54\u003c\/p\u003e \u003cp\u003e4.3.4 Fragmentation Mode 55\u003c\/p\u003e \u003cp\u003e4.3.5 Emerging MS Techniques 56\u003c\/p\u003e \u003cp\u003e4.3.5.1 MS Imaging 56\u003c\/p\u003e \u003cp\u003e4.3.5.2 Other Surface Analysis MS Techniques 58\u003c\/p\u003e \u003cp\u003e4.4 Summary and Future Perspectives 58\u003c\/p\u003e \u003cp\u003eReferences 59\u003c\/p\u003e \u003cp\u003e5 Comparison Between LC–MS and Ligand]Binding Assay Approaches for Biomarker Quantification 65\u003cbr\u003e\u003ci\u003eQingQing Wang, Lili Guo, and Ian A. Blair\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e5.1 General Considerations: LBAs or LC–MS Assays 65\u003c\/p\u003e \u003cp\u003e5.2 General Quantification Approaches 66\u003c\/p\u003e \u003cp\u003e5.3 Analytical Issues Specifically Related to LBAs 67\u003c\/p\u003e \u003cp\u003e5.3.1 There Is No Sample Pretreatment in Most LBAs 67\u003c\/p\u003e \u003cp\u003e5.3.2 It Is Hard to Distinguish Biomarkers and Their Variants by LBAs 68\u003c\/p\u003e \u003cp\u003e5.4 Analytical Features Specifically Related to LC–MS Methods 68\u003c\/p\u003e \u003cp\u003e5.4.1 Proper Sample Preparation Generates Better Data 69\u003c\/p\u003e \u003cp\u003e5.4.2 Biomarkers and Their Variants Can Be Distinguished 69\u003c\/p\u003e \u003cp\u003e5.4.3 Stable Isotope]Labeled Internal Standard Used for Assuring the Assay Accuracy 71\u003c\/p\u003e \u003cp\u003e5.5 Case Studies: Comparison Between ELISA and LC–MS 72\u003c\/p\u003e \u003cp\u003e5.5.1 Steroid Analysis 72\u003c\/p\u003e \u003cp\u003e5.5.2 Apolipoprotein A1 74\u003c\/p\u003e \u003cp\u003e5.6 Summary and Future Perspective 74\u003c\/p\u003e \u003cp\u003eReferences 74\u003c\/p\u003e \u003cp\u003e6 Sample Preparation Methods for Targeted Biomarker Quantification by LC]MS 79\u003cbr\u003e\u003ci\u003eShichen Shen, Bo An, and Jun Qu\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e6.1 Introduction 79\u003c\/p\u003e \u003cp\u003e6.2 Sample Preparation Strategies for Small Molecule Biomarkers 79\u003c\/p\u003e \u003cp\u003e6.2.1 Primary Issues to Address for Sample Preparation 80\u003c\/p\u003e \u003cp\u003e6.2.1.1 Matrix Effects 80\u003c\/p\u003e \u003cp\u003e6.2.1.2 Sensitivity and Selectivity 81\u003c\/p\u003e \u003cp\u003e6.2.1.3 Selection of Calibration Methods 82\u003c\/p\u003e \u003cp\u003e6.2.2 Sample Preparation Techniques 82\u003c\/p\u003e \u003cp\u003e6.2.2.1 Dilute]and]Shoot 82\u003c\/p\u003e \u003cp\u003e6.2.2.2 Protein Precipitation (PPT) 82\u003c\/p\u003e \u003cp\u003e6.2.2.3 Liquid–Liquid Extraction (LLE) 82\u003c\/p\u003e \u003cp\u003e6.2.2.4 Solid]Phase Extraction (SPE) 84\u003c\/p\u003e \u003cp\u003e6.3 Sample Preparation Strategies for Macromolecule Biomarkers 86\u003c\/p\u003e \u003cp\u003e6.3.1 Considerations for Sample Preparation 86\u003c\/p\u003e \u003cp\u003e6.3.1.1 Matrix Effects 86\u003c\/p\u003e \u003cp\u003e6.3.1.2 Recovery of the Signature Peptide from the Target Analyte 86\u003c\/p\u003e \u003cp\u003e6.3.1.3 Selection of Calibration Methods 88\u003c\/p\u003e \u003cp\u003e6.3.1.4 Sensitivity and Selectivity 89\u003c\/p\u003e \u003cp\u003e6.3.2 Methods for Protein Extraction 89\u003c\/p\u003e \u003cp\u003e6.3.3 Methods for Protein and Peptide Enrichment 89\u003c\/p\u003e \u003cp\u003e6.3.3.1 Immunoaffinity Capture (IC) 90\u003c\/p\u003e \u003cp\u003e6.3.3.2 Sample Fractionation 90\u003c\/p\u003e \u003cp\u003e6.3.3.3 Depletion of High Abundance Proteins (HAPs) 91\u003c\/p\u003e \u003cp\u003e6.3.4 Methods for Protein Denaturation, Reduction, and Alkylation 92\u003c\/p\u003e \u003cp\u003e6.3.5 Methods for Proteolytic Digestion 93\u003c\/p\u003e \u003cp\u003e6.4 Conclusive\u003c\/p\u003e \u003cp\u003eRemarks 94\u003c\/p\u003e \u003cp\u003eReferences 95\u003c\/p\u003e \u003cp\u003e7 Overcome the Endogenous Levels in Biomarker Quantitation Using LC–MS 107\u003cbr\u003e\u003ci\u003eGuowen Liu\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e7.1 Introduction 107\u003c\/p\u003e \u003cp\u003e7.2 How Does Matrix Effect Affect Quantitation? 108\u003c\/p\u003e \u003cp\u003e7.3 Commonly Used Strategies 109\u003c\/p\u003e \u003cp\u003e7.3.1 Authentic Analyte in Authentic Matrix (Standard Addition) 109\u003c\/p\u003e \u003cp\u003e7.3.2 Surrogate Analyte in Authentic Matrix 109\u003c\/p\u003e \u003cp\u003e7.3.3 Authentic Analyte in Surrogate Matrix 112\u003c\/p\u003e \u003cp\u003e7.4 Discussions and Future Perspectives 114\u003c\/p\u003e \u003cp\u003eReferences 115\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart II Challenges and Approaches 119\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e8 Sample Collection for Targeted Biomarker Quantitation by LC–MS 121\u003cbr\u003e\u003ci\u003eYuzhong Deng and Xiaorong Liang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e8.1 Introduction 121\u003c\/p\u003e \u003cp\u003e8.2 Timing of Biomarker Sample Collection 121\u003c\/p\u003e \u003cp\u003e8.3 Matrix Type 122\u003c\/p\u003e \u003cp\u003e8.3.1 Serum or Plasma 122\u003c\/p\u003e \u003cp\u003e8.3.2 Urine 123\u003c\/p\u003e \u003cp\u003e8.3.3 Tissue 123\u003c\/p\u003e \u003cp\u003e8.4 Collection Methods 124\u003c\/p\u003e \u003cp\u003e8.4.1 Plasma Sample Collection 124\u003c\/p\u003e \u003cp\u003e8.4.1.1 Anticoagulants 124\u003c\/p\u003e \u003cp\u003e8.4.1.2 Stabilizing Agents 125\u003c\/p\u003e \u003cp\u003e8.4.1.3 Temperature and Timing before Initial Processing 126\u003c\/p\u003e \u003cp\u003e8.4.1.4 Endogenous Degradation 126\u003c\/p\u003e \u003cp\u003e8.4.2 Urine Sample Collection 127\u003c\/p\u003e \u003cp\u003e8.4.3 Tissue Sample Collection 128\u003c\/p\u003e \u003cp\u003e8.5 Sample Storage Stability 128\u003c\/p\u003e \u003cp\u003e8.5.1 Storage of Blood]Derived Fluids and Urine Samples 128\u003c\/p\u003e \u003cp\u003e8.5.2 Storage of Tissue Samples 129\u003c\/p\u003e \u003cp\u003e8.5.3 Freeze\/Thaw Effect 129\u003c\/p\u003e \u003cp\u003e8.6 Summary 129\u003c\/p\u003e \u003cp\u003eReferences 130\u003c\/p\u003e \u003cp\u003e9 Nonspecific Binding in LC–MS Bioanalysis 137\u003cbr\u003e\u003ci\u003eAimin Tan and John C. Fanaras\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e9.1 Introduction 137\u003c\/p\u003e \u003cp\u003e9.2 Identification and Evaluation of NSB 137\u003c\/p\u003e \u003cp\u003e9.2.1 Common Scenarios and Indicators for Potential NSB Issues 137\u003c\/p\u003e \u003cp\u003e9.2.2 Confirmation\/Identification and Evaluation of NSB 138\u003c\/p\u003e \u003cp\u003e9.2.3 NSB versus Stability Issue 139\u003c\/p\u003e \u003cp\u003e9.3 Causes for NSB 140\u003c\/p\u003e \u003cp\u003e9.4 Overcoming NSB Challenges 140\u003c\/p\u003e \u003cp\u003e9.4.1 Solubilization of Compounds 140\u003c\/p\u003e \u003cp\u003e9.4.2 Overview of Measures for Overcoming NSB Challenges 141\u003c\/p\u003e \u003cp\u003e9.4.3 Application Examples 143\u003c\/p\u003e \u003cp\u003e9.5 Conclusion 144\u003c\/p\u003e \u003cp\u003eReferences 146\u003c\/p\u003e \u003cp\u003e10 Strategies for Improving Sensitivity for Targeted Quantitation by LC–MS 149\u003cbr\u003e\u003ci\u003eLong Yuan and Qin C. Ji\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e10.1 Introduction 149\u003c\/p\u003e \u003cp\u003e10.2 Sample Preparation Strategies for Improving Sensitivity 150\u003c\/p\u003e \u003cp\u003e10.2.1 Protein Precipitation 151\u003c\/p\u003e \u003cp\u003e10.2.2 Liquid–Liquid Extraction 152\u003c\/p\u003e \u003cp\u003e10.2.3 Solid]Phase Extraction 153\u003c\/p\u003e \u003cp\u003e10.2.4 Immunoaffinity Extraction 154\u003c\/p\u003e \u003cp\u003e10.2.5 Chemical Derivatization 155\u003c\/p\u003e \u003cp\u003e10.2.6 Online Sample Preparation 155\u003c\/p\u003e \u003cp\u003e10.3 LC Separation Strategies for Improving Sensitivity 156\u003c\/p\u003e \u003cp\u003e10.3.1 Optimization of Mobile Phase 156\u003c\/p\u003e \u003cp\u003e10.3.2 2D]LC 157\u003c\/p\u003e \u003cp\u003e10.3.3 Low]Flow LC 157\u003c\/p\u003e \u003cp\u003e10.4 MS Detection Strategies for Improving Sensitivity 160\u003c\/p\u003e \u003cp\u003e10.4.1 SRM 160\u003c\/p\u003e \u003cp\u003e10.4.2 High]Resolution Mass Spectrometry (HRMS) 162\u003c\/p\u003e \u003cp\u003e10.4.3 IMS 163\u003c\/p\u003e \u003cp\u003e10.5 Conclusions 163\u003c\/p\u003e \u003cp\u003eReferences 163\u003c\/p\u003e \u003cp\u003e11 Strategies to Improve Specificity for Targeted Biomarker Quantitation by LC–MS 171\u003cbr\u003e\u003ci\u003eYuan]Qing Xia and Jeffrey D. Miller\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e11.1 Introduction 171\u003c\/p\u003e \u003cp\u003e11.2 Differential Mobility Spectrometry 171\u003c\/p\u003e \u003cp\u003e11.3 High]Resolution Mass Spectrometry 175\u003c\/p\u003e \u003cp\u003e11.4 Conclusions 180\u003c\/p\u003e \u003cp\u003eReferences 180\u003c\/p\u003e \u003cp\u003e12 Biomarker Quantitation Using Relative Approaches 183\u003cbr\u003e\u003ci\u003eShane M. Lamos and Katrina E. Wiesner\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e12.1 Introduction 183\u003c\/p\u003e \u003cp\u003e12.2 Relative Quantitation Isotope Labeling Approaches 183\u003c\/p\u003e \u003cp\u003e12.2.1 Enzymatic Isotopic Incorporation 183\u003c\/p\u003e \u003cp\u003e12.2.2 Metabolic Isotopic Incorporation 185\u003c\/p\u003e \u003cp\u003e12.2.3 Chemical Labeling (Nonisobaric) 187\u003c\/p\u003e \u003cp\u003e12.2.4 Chemical Labeling (Isobaric) 188\u003c\/p\u003e \u003cp\u003e12.3 Conclusions 191\u003c\/p\u003e \u003cp\u003eReferences 192\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart III Applications 195\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e13 Targeted Quantification of Amino Acid Biomarkers Using LC]MS 197\u003cbr\u003e\u003ci\u003eBarry R. Jones, Raymond F. Biondolillo, and John E. Buckholz\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e13.1 Introduction 197\u003c\/p\u003e \u003cp\u003e13.2 Amino Acids as Biomarkers 198\u003c\/p\u003e \u003cp\u003e13.2.1 Biomarker of Heart Failure 199\u003c\/p\u003e \u003cp\u003e13.2.2 Citrulline as Biomarker of Intestinal Failure 199\u003c\/p\u003e \u003cp\u003e13.2.3 Oncological Biomarkers 200\u003c\/p\u003e \u003cp\u003e13.2.4 Branched]Chain Amino Acids in Diabetes and Cancer 200\u003c\/p\u003e \u003cp\u003e13.2.5 Inborn Errors of Metabolism 200\u003c\/p\u003e \u003cp\u003e13.2.6 Biomarker of Phenylketonuria (PKU) 201\u003c\/p\u003e \u003cp\u003e13.2.7 Amino Acid Supplementation 201\u003c\/p\u003e \u003cp\u003e13.3 Methods of Measurement 201\u003c\/p\u003e \u003cp\u003e13.3.1 LC]MS Considerations for Measurement of 2]Hydroxyglutarate 202\u003c\/p\u003e \u003cp\u003e13.4 Accuracy, Precision, Selectivity, and Stability Considerations 203\u003c\/p\u003e \u003cp\u003e13.4.1 Accuracy 203\u003c\/p\u003e \u003cp\u003e13.4.1.1 Accuracy: Surrogate Matrix 203\u003c\/p\u003e \u003cp\u003e13.4.1.2 Accuracy: Surrogate Analyte 205\u003c\/p\u003e \u003cp\u003e13.4.1.3 Surrogate Matrix\/Analyte Considerations for Multiplexed Amino Acid Assays 205\u003c\/p\u003e \u003cp\u003e13.4.2 Precision 206\u003c\/p\u003e \u003cp\u003e13.4.3 Selectivity 206\u003c\/p\u003e \u003cp\u003e13.4.4 Stability 207\u003c\/p\u003e \u003cp\u003e13.5 Assay Design 207\u003c\/p\u003e \u003cp\u003e13.6 Conclusion 207\u003c\/p\u003e \u003cp\u003eReferences 208\u003c\/p\u003e \u003cp\u003e14 Targeted Quantification of Peptide Biomarkers: A Case Study of Amyloid Peptides 211\u003cbr\u003e\u003ci\u003eLieve Dillen, Marc De Meulder, and Tom Verhaeghe\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e14.1 Overview 211\u003c\/p\u003e \u003cp\u003e14.2 Challenges and Approaches 212\u003c\/p\u003e \u003cp\u003e14.2.1 Multiply Charged Ions: SRM Versus HRMS 212\u003c\/p\u003e \u003cp\u003e14.2.2 Adsorption–Solubility–Stability Aspects 214\u003c\/p\u003e \u003cp\u003e14.2.3 Blank Matrix–Internal Standard–Surrogate Analytes 214\u003c\/p\u003e \u003cp\u003e14.2.4 Extraction–Sample Pretreatment 215\u003c\/p\u003e \u003cp\u003e14.3 Application to the Quantification of Alzheimer’s Disease Biomarkers 216\u003c\/p\u003e \u003cp\u003e14.3.1 Introduction: Amyloid Peptides in CSF as Biomarkers for Alzheimer’s Disease 216\u003c\/p\u003e \u003cp\u003e14.3.2 LC]MS\/MS Method for Analysis of Amyloid Peptides in CSF in Support of Preclinical Development 216\u003c\/p\u003e \u003cp\u003e14.3.3 LC]MS\/MS Method for Analysis of Amyloid Peptides in CSF in Support of Clinical Development 217\u003c\/p\u003e \u003cp\u003e14.3.4 Comparison of Immunoassay and UHPLC]MS\/MS: Are the Results Comparable? 219\u003c\/p\u003e \u003cp\u003e14.4 Conclusion 222\u003c\/p\u003e \u003cp\u003eReferences 222\u003c\/p\u003e \u003cp\u003e15 Targeted Protein Biomarker Quantitation by LC]MS 227\u003cbr\u003e\u003ci\u003eYongle Pang, Chuan Shi, and Wenying Jian\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e15.1 Introduction 227\u003c\/p\u003e \u003cp\u003e15.2 Sample Preparation for Targeted Protein Biomarker Quantitation 231\u003c\/p\u003e \u003cp\u003e15.2.1 Protein Precipitation 232\u003c\/p\u003e \u003cp\u003e15.2.2 Solid Phase Extraction 232\u003c\/p\u003e \u003cp\u003e15.2.3 Abundant Protein Depletion 232\u003c\/p\u003e \u003cp\u003e15.2.4 Affinity Enrichment 233\u003c\/p\u003e \u003cp\u003e15.3 “Bottom]Up” Approach for Targeted Protein Biomarker Quantitation Using LC]MS 233\u003c\/p\u003e \u003cp\u003e15.3.1 Surrogate Peptide Selection 233\u003c\/p\u003e \u003cp\u003e15.3.2 Sample Pretreatment Prior to Proteolytic Digestion 234\u003c\/p\u003e \u003cp\u003e15.3.3 Proteolytic Digestion 234\u003c\/p\u003e \u003cp\u003e15.3.4 LC]MS Analysis 235\u003c\/p\u003e \u003cp\u003e15.4 “Top Down” Approach for Targeted Protein Biomarker Quantitation Using LC]MS 235\u003c\/p\u003e \u003cp\u003e15.5 Key Considerations in Targeted Protein Biomarker Quantitation Using LC]MS 236\u003c\/p\u003e \u003cp\u003e15.5.1 Preanalytical Considerations 236\u003c\/p\u003e \u003cp\u003e15.5.2 Internal Standard 236\u003c\/p\u003e \u003cp\u003e15.5.3 Reference Standard 237\u003c\/p\u003e \u003cp\u003e15.5.4 Improving Sensitivity of the Assay 238\u003c\/p\u003e \u003cp\u003e15.5.5 Improving Throughput of the Assay 238\u003c\/p\u003e \u003cp\u003e15.5.6 Correlating MS Data with LBA Data 239\u003c\/p\u003e \u003cp\u003e15.6 Summary and Future Perspectives 239\u003c\/p\u003e \u003cp\u003eReferences 240\u003c\/p\u003e \u003cp\u003e16 Glycoprotein Biomarkers 245\u003cbr\u003e\u003ci\u003eShuwei Li, Stefani N. Thomas, and Shuang Yang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e16.1 Introduction 245\u003c\/p\u003e \u003cp\u003e16.2 Technologies for Glycoprotein Analysis 246\u003c\/p\u003e \u003cp\u003e16.2.1 Glycoprotein Enrichment 246\u003c\/p\u003e \u003cp\u003e16.2.1.1 Techniques for the Enrichment of Glycoproteins 246\u003c\/p\u003e \u003cp\u003e16.2.1.2 Hybrid Chemical Metabolic Labeling 248\u003c\/p\u003e \u003cp\u003e16.2.2 Glycan Analysis 251\u003c\/p\u003e \u003cp\u003e16.2.2.1 In]Solution Glycan Analysis 251\u003c\/p\u003e \u003cp\u003e16.2.2.2 Solid]Phase Glycan Analysis 252\u003c\/p\u003e \u003cp\u003e16.2.3 Automated Platform for Processing Clinical Specimens 252\u003c\/p\u003e \u003cp\u003e16.2.4 MS Analysis of Glycoproteins 254\u003c\/p\u003e \u003cp\u003e16.2.4.1 Bottom]Up Approaches 254\u003c\/p\u003e \u003cp\u003e16.2.4.2 Top]Down Approaches 254\u003c\/p\u003e \u003cp\u003e16.2.4.3 MS\/MS Fragmentation Methods for Glycopeptides 254\u003c\/p\u003e \u003cp\u003e16.3 Glycoprotein Biomarker Quantification Using LC]MS 255\u003c\/p\u003e \u003cp\u003e16.3.1 Quantification by Stable Isotope Labeling 255\u003c\/p\u003e \u003cp\u003e16.3.2 Metabolic Labeling Strategies 255\u003c\/p\u003e \u003cp\u003e16.3.3 Label]Free Glycoprotein Quantification 257\u003c\/p\u003e \u003cp\u003e16.3.4 Methods for Targeted Quantification Using LC]MS\/MS 259\u003c\/p\u003e \u003cp\u003e16.4 Protein Biomarkers for Clinical Applications 259\u003c\/p\u003e \u003cp\u003e16.4.1 FDA]Approved Glycoprotein Biomarkers 259\u003c\/p\u003e \u003cp\u003e16.4.2 Classes of Biomarkers 260\u003c\/p\u003e \u003cp\u003e16.4.3 New Glycoprotein Biomarker Discovery 260\u003c\/p\u003e \u003cp\u003e16.5 Summary and Future Direction 264\u003c\/p\u003e \u003cp\u003eReferences 265\u003c\/p\u003e \u003cp\u003e17 Targeted Lipid Biomarker Quantitation Using Liquid Chromatography–Mass Spectrometry (LC–MS) 273\u003cbr\u003e\u003ci\u003eAshkan Salamatipour, Ian A. Blair, and Clementina Mesaros\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e17.1 Introduction of Lipids 273\u003c\/p\u003e \u003cp\u003e17.2 LC–MS Analysis of Lipids 276\u003c\/p\u003e \u003cp\u003e17.3 Examples of LC–MS Analysis of Lipids 278\u003c\/p\u003e \u003cp\u003e17.3.1 Omega]6]Derived Eicosanoids 278\u003c\/p\u003e \u003cp\u003e17.3.2 Docosahexaenoic Acid (DHA) 279\u003c\/p\u003e \u003cp\u003e17.3.3 N]Acylethanolamines (NAEs) and Eicosanoids 281\u003c\/p\u003e \u003cp\u003e17.3.4 Arachidonic Acid (AA) 282\u003c\/p\u003e \u003cp\u003e17.4 Summary and Future Directions 283\u003c\/p\u003e \u003cp\u003eReferences 283\u003c\/p\u003e \u003cp\u003e18 Targeted LC–MS Quantification of Androgens and Estrogens for Biomarker Development 289\u003cbr\u003e\u003ci\u003eDaniel Tamae\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e18.1 Introduction 289\u003c\/p\u003e \u003cp\u003e18.1.1 History of Estrogen and Androgen Quantification 289\u003c\/p\u003e \u003cp\u003e18.1.2 Androgen Biosynthesis and Metabolism 290\u003c\/p\u003e \u003cp\u003e18.1.3 Estrogen Biosynthesis and Metabolism 290\u003c\/p\u003e \u003cp\u003e18.2 Current Considerations in Biomarker Validation 292\u003c\/p\u003e \u003cp\u003e18.3 Current Considerations in LC–MS Method Development 293\u003c\/p\u003e \u003cp\u003e18.3.1 Chromatography 293\u003c\/p\u003e \u003cp\u003e18.3.2 Direct Detection Methods 293\u003c\/p\u003e \u003cp\u003e18.3.3 Derivatization Strategies 294\u003c\/p\u003e \u003cp\u003e18.3.4 Stable Isotope Standards 295\u003c\/p\u003e \u003cp\u003e18.3.5 Hydrolysis of Conjugated Steroids 296\u003c\/p\u003e \u003cp\u003e18.4 Clinical Application of LC–MS Quantification of Estrogens and Androgens 296\u003c\/p\u003e \u003cp\u003e18.4.1 Reference Ranges of Estrogens and Androgens 296\u003c\/p\u003e \u003cp\u003e18.4.2 Estrogens in Postmenopausal Women and Low Androgens in Aging Men 297\u003c\/p\u003e \u003cp\u003e18.4.3 Estrogens and Breast Cancer 297\u003c\/p\u003e \u003cp\u003e18.4.4 Androgens and Prostate Cancer 298\u003c\/p\u003e \u003cp\u003e18.5 Conclusion and Perspective 301\u003c\/p\u003e \u003cp\u003eReferences 301\u003c\/p\u003e \u003cp\u003e19 Steroid Biomarkers 307\u003cbr\u003e\u003ci\u003eMike (Qingtao) Huang, Shefali Patel, and Zhongping (John) Lin\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e19.1 Introduction 307\u003c\/p\u003e \u003cp\u003e19.2 Sterols as Endogenous Biomarkers and Their Quantitation 307\u003c\/p\u003e \u003cp\u003e19.2.1 4β]OHC as a P450 3A4\/5 Endogenous Biomarker 307\u003c\/p\u003e \u003cp\u003e19.2.2 Quantitation of 4β]OHC in Human and Animal Species 310\u003c\/p\u003e \u003cp\u003e19.2.3 24S]OHC and 27]OHC as Biomarkers 311\u003c\/p\u003e \u003cp\u003e19.2.4 Quantitation of 24S]OHC and 27]OHC 312\u003c\/p\u003e \u003cp\u003e19.3 Cortisol and 6 β]Hydroxycortisol (6β]HC) as Biomarkers and Their Quantitation 312\u003c\/p\u003e \u003cp\u003e19.3.1 Cortisol and 6β]HC as Biomarkers 312\u003c\/p\u003e \u003cp\u003e19.3.2 Measurement of Cortisol and 6β]HC 313\u003c\/p\u003e \u003cp\u003e19.3.2.1 Measurement of Cortisol in Serum 313\u003c\/p\u003e \u003cp\u003e19.3.2.2 Measurement of Cortisol and 6β]HC in Urine 314\u003c\/p\u003e \u003cp\u003e19.3.2.3 Measurement of Cortisol in Saliva and Hair 315\u003c\/p\u003e \u003cp\u003e19.4 Summary 316\u003c\/p\u003e \u003cp\u003eReferences 316\u003c\/p\u003e \u003cp\u003e20 Bile Acids as Biomarkers 321\u003cbr\u003e\u003ci\u003eClara John, Philipp Werner, Joerg Heeren, and Markus Fischer\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e20.1 Introduction 321\u003c\/p\u003e \u003cp\u003e20.2 Analytical Platform for Bile Acids 323\u003c\/p\u003e \u003cp\u003e20.3 Summary 327\u003c\/p\u003e \u003cp\u003eReferences 327\u003c\/p\u003e \u003cp\u003e21 Biomarkers for Vitamin Status and Deficiency: LC]MS Based Approach 331\u003cbr\u003e\u003ci\u003eStanley (Weihua) Zhang and Jonathan Crowther\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e21.1 Introduction to Vitamin and Vitamin Deficiency 331\u003c\/p\u003e \u003cp\u003e21.2 Detection of Vitamin D by LC]MS\/MS and Comparison with Other Methods 332\u003c\/p\u003e \u003cp\u003e21.2.1 Vitamin D and Vitamin D Deficiency 332\u003c\/p\u003e \u003cp\u003e21.2.2 Target the Right Metabolites 332\u003c\/p\u003e \u003cp\u003e21.2.3 Analytical Challenges 332\u003c\/p\u003e \u003cp\u003e21.2.4 History of Vitamin D Quantification Assays 333\u003c\/p\u003e \u003cp\u003e21.2.5 Quantification of 25(OH)D by LC]MS\/MS 334\u003c\/p\u003e \u003cp\u003e21.2.5.1 Considerations in Assay Development and Validation 334\u003c\/p\u003e \u003cp\u003e21.2.5.2 Sample Preparation 335\u003c\/p\u003e \u003cp\u003e21.2.5.3 LC]MS\/MS 335\u003c\/p\u003e \u003cp\u003e21.2.5.4 Method Comparison and Standardization 336\u003c\/p\u003e \u003cp\u003e21.3 Other Vitamin Biomarkers 338\u003c\/p\u003e \u003cp\u003e21.3.1 Retinol: Biomarkers of Vitamin A Status and Deficiency 338\u003c\/p\u003e \u003cp\u003e21.3.2 Folic Acid: Biomarkers for Vitamin B9 Dietary Intake 339\u003c\/p\u003e \u003cp\u003e21.3.3 Vitamin C: An Appropriate Biomarker of Vitamin C Intake 340\u003c\/p\u003e \u003cp\u003e21.4 Conclusions and Perspectives 340\u003c\/p\u003e \u003cp\u003eReferences 341\u003c\/p\u003e \u003cp\u003e22 Quantitation of Acyl]Coenzyme A Thioesters as Metabolic Biomarkers 347\u003cbr\u003e\u003ci\u003eNathaniel Snyder\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e22.1 Introduction 347\u003c\/p\u003e \u003cp\u003e22.2 Structure and Function of Acyl]CoAs 347\u003c\/p\u003e \u003cp\u003e22.3 Detection and Quantitation of Acyl]CoAs 349\u003c\/p\u003e \u003cp\u003e22.4 Acyl]CoA Analysis for Current Drug Targets 352\u003c\/p\u003e \u003cp\u003e22.5 Acyl]CoAs as Biomarkers in Metabolic Disease 352\u003c\/p\u003e \u003cp\u003e22.6 The Involvement of Acyl]CoAs in Drug Metabolism 353\u003c\/p\u003e \u003cp\u003eReferences 353\u003c\/p\u003e \u003cp\u003e23 Neurotransmitter Biomarkers 357\u003cbr\u003e\u003ci\u003eGuodong Zhang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e23.1 Introduction 357\u003c\/p\u003e \u003cp\u003e23.2 Chromatographic Platforms of Biological Measurement for Neurotransmitters 358\u003c\/p\u003e \u003cp\u003e23.2.1 Challenges for Neurotransmitter Measurement 358\u003c\/p\u003e \u003cp\u003e23.2.2 LBA, LC, GC, and CE 358\u003c\/p\u003e \u003cp\u003e23.2.3 LC–MS\/MS 359\u003c\/p\u003e \u003cp\u003e23.3 Bioanalytical Methodologies 359\u003c\/p\u003e \u003cp\u003e23.3.1 Sample Preparation Strategies 359\u003c\/p\u003e \u003cp\u003e23.3.2 Sensitivity and Chromatography Enhancement by Chemical Derivatization Using LC]MS\/MS 362\u003c\/p\u003e \u003cp\u003e23.3.3 Chromatographic Strategies for LC]MS\/MS Assays 362\u003c\/p\u003e \u003cp\u003e23.3.4 NTs Stability and Sample Collection 363\u003c\/p\u003e \u003cp\u003e23.3.5 Case Studies 367\u003c\/p\u003e \u003cp\u003e23.4 Conclusion 367\u003c\/p\u003e \u003cp\u003eReferences 367\u003c\/p\u003e \u003cp\u003e24 Targeted Quantification of Carbohydrate Biomarkers Using LC–MS 371\u003cbr\u003e\u003ci\u003eCong Wei and Hong Gao\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e24.1 Introduction 371\u003c\/p\u003e \u003cp\u003e24.2 Overview 371\u003c\/p\u003e \u003cp\u003e24.2.1 Clinical Diagnostic Carbohydrate Biomarkers 371\u003c\/p\u003e \u003cp\u003e24.2.2 Overview of Bioanalytical Analysis of Carbohydrate Biomarker 372\u003c\/p\u003e \u003cp\u003e24.3 Bioanalytical Method Development for Carbohydrate Biomarkers 374\u003c\/p\u003e \u003cp\u003e24.3.1 Sample Preparation 374\u003c\/p\u003e \u003cp\u003e24.3.1.1 Sample Preparation by Solid]Phase Extraction (SPE) 374\u003c\/p\u003e \u003cp\u003e24.3.1.2 Sample Preparation by Liquid–Liquid Extraction (LLE) 376\u003c\/p\u003e \u003cp\u003e24.3.1.3 Sample Preparation by Derivatization 378\u003c\/p\u003e \u003cp\u003e24.3.1.4 Sample Preparation by Enzymatic Digestion or Chemical Reduction 378\u003c\/p\u003e \u003cp\u003e24.3.2 Chromatography and Column Options 380\u003c\/p\u003e \u003cp\u003e24.3.2.1 HILIC for LC–MS\/MS Bioanalysis 381\u003c\/p\u003e \u003cp\u003e24.3.2.2 Porous Graphic Hypercarb Chromatography for LC–MS\/MS Bioanalysis 381\u003c\/p\u003e \u003cp\u003e24.3.2.3 Reversed]Phase Chromatography for LC–MS\/MS Bioanalysis 382\u003c\/p\u003e \u003cp\u003e24.3.2.4 Reversed]Phase Ion]Pair Chromatography for LC–MS Bioanalysis 382\u003c\/p\u003e \u003cp\u003e24.3.3 LC–MS\/MS Analysis 383\u003c\/p\u003e \u003cp\u003e24.4 Conclusions 384\u003c\/p\u003e \u003cp\u003eReferences 384\u003c\/p\u003e \u003cp\u003e25 Nucleoside\/Nucleotide Biomarkers 389\u003cbr\u003e\u003ci\u003eGuodong Zhang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e25.1 Introduction 389\u003c\/p\u003e \u003cp\u003e25.2 Chromatographic Platforms for Nucleosides\/Nucleotides 390\u003c\/p\u003e \u003cp\u003e25.2.1 Challenges for Nucleosides and Nucleotides Measurement 390\u003c\/p\u003e \u003cp\u003e25.2.2 Conventional Immunoassays, CE, GC and HPLC 390\u003c\/p\u003e \u003cp\u003e25.2.3 LC–MS\/MS 391\u003c\/p\u003e \u003cp\u003e25.3 Bioanalytical Methodologies 391\u003c\/p\u003e \u003cp\u003e25.3.1 Sample Preparation Strategies 391\u003c\/p\u003e \u003cp\u003e25.3.2 Chromatographic Strategies for LC–MS\/MS Assays 394\u003c\/p\u003e \u003cp\u003e25.4 Nucleoside\/Nucleotide Biomarkers and Case Studies 398\u003c\/p\u003e \u003cp\u003e25.5 Conclusion 399\u003c\/p\u003e \u003cp\u003eReferences 402\u003c\/p\u003e \u003cp\u003e26 LC–MS of RNA Biomarkers 407\u003cbr\u003e\u003ci\u003eMichael G. Bartlett, Babak Basiri, and Ning Li\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e26.1 Introduction 407\u003c\/p\u003e \u003cp\u003e26.2 Role in Disease and Therapeutics 408\u003c\/p\u003e \u003cp\u003e26.3 Role of Mass Spectrometry in RNA Biomarkers 409\u003c\/p\u003e \u003cp\u003e26.4 LC–MS Approaches for RNA Determination 411\u003c\/p\u003e \u003cp\u003e26.4.1 Sample Preparation 411\u003c\/p\u003e \u003cp\u003e26.4.2 Ion]Pair Chromatography 413\u003c\/p\u003e \u003cp\u003e26.4.3 Capillary Chromatography 414\u003c\/p\u003e \u003cp\u003e26.4.4 Liquid Chromatography–Inductively Coupled Plasma Mass Spectrometry 415\u003c\/p\u003e \u003cp\u003e26.5 Case Studies 415\u003c\/p\u003e \u003cp\u003e26.5.1 Single Nucleotide Polymorphisms as Biomarkers 415\u003c\/p\u003e \u003cp\u003e26.5.2 Small Interfering RNA Determination 416\u003c\/p\u003e \u003cp\u003e26.5.3 MicroRNA Determination 416\u003c\/p\u003e \u003cp\u003eReferences 418\u003c\/p\u003e \u003cp\u003eIndex 425\u003c\/p\u003e","brand":"John Wiley \u0026 Sons Inc","offers":[{"title":"Default Title","offer_id":49406986092887,"sku":"9781119103066","price":152.06,"currency_code":"GBP","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0817\/1739\/5799\/files\/9781119103066.jpg?v=1730497793","url":"https:\/\/bookcurl.com\/products\/targeted-biomarker-quantitation-by-lcms-9781119103066","provider":"Book Curl","version":"1.0","type":"link"}