Cover
List of Contributors
Preface
List of Abbreviations
Part I: Current Sample Preparation Techniques in LC‐MS Bioanalysis
1. 1 Basic Sample Preparation Techniques in LC‐MS Bioanalysis
  1. 1.1 Introduction
  2. 1.2 Physicochemical Properties of Drugs and Their Metabolites
  3. 1.3 Pre‐analytical Variables of Analyte(s) of Interest in Biological Matrix
  4. 1.4 Most Commonly Used Sample Preparation Methods in LC‐MS Bioanalysis
  5. References
2. 2 Online Extraction and Column Switching Techniques in LC‐MS Bioanalysis
  1. 2.1 Introduction
  2. 2.2 System Configuration
  3. 2.3 Commonly Used Online Extraction Techniques
  4. 2.4 Considerations for Utilizing Online Extraction Techniques
  5. 2.5 Summary
  6. References
3. 3 Equilibrium Dialysis, Ultracentrifugation, and Ultrafiltration in LC‐MS Bioanalysis
  1. 3.1 Introduction
  2. 3.2 Challenges and Considerations
  3. 3.3 Experimental Procedures
  4. 3.4 Summary
  5. References
4. 4 Phospholipid Depletion Techniques in LC‐MS Bioanalysis
  1. 4.1 Introduction
  2. 4.2 Impact of Phospholipids on Bioanalytical Methods
  3. 4.3 Investigating Matrix Effects Associated with Phospholipids
  4. 4.4 Minimizing Matrix Effects Associated with Phospholipids
  5. 4.5 Removing Phospholipids Prior to LC‐MS Analysis
  6. 4.6 Example Methods that Demonstrate Successful Phospholipid Removal
  7. 4.7 Conclusions
  8. Acknowledgement
  9. References
5. 5 Salting‐out Assisted Liquid–Liquid Extraction (SALLE) in LC‐MS Bioanalysis
  1. 5.1 Introduction
  2. 5.2 Considerations in Developing a SALLE Method
  3. 5.3 Combination of SALLE with Other Extraction Techniques
  4. 5.4 Matrix Effect in SALLE
  5. 5.5 Miniaturization and Automatization
  6. 5.6 Summary
  7. References
6. 6 Supported Liquid Extraction (SLE) in LC‐MS Bioanalysis
  1. 6.1 Introduction
  2. 6.2 Principle of SLE
  3. 6.3 Advantages and Limitation of SLE in Quantitative LC‐MS Bioanalysis
  4. 6.4 Key Consideration in Developing Robust SLE‐LC‐MS Bioanalytical Method
  5. 6.5 Representative Protocols
  6. 6.6 Summary
  7. References
7. 7 Immunocapture in LC‐MS Bioanalysis
  1. 7.1 Introduction
  2. 7.2 Experimental Workflow and Optimization
  3. 7.3 Considerations on the Selection of Capture Reagents and the Limitations
  4. 7.4 Platforms for Immunocapture
  5. 7.5 Internal Standard Selection
  6. 7.6 Performance Evaluation
  7. 7.7 Applications and Representative Protocols
  8. 7.8 Validation Criteria and Regulatory Considerations
  9. 7.9 Summary
  10. References
8. 8 Microextraction Techniques in LC‐MS Bioanalysis
  1. 8.1 Introduction
  2. 8.2 Solid‐Phase Microextraction
  3. 8.3 Liquid‐Phase Microextraction
  4. 8.4 Summary
  5. Acknowledgements
  6. References
9. 9 Microsampling Applications with LC‐MS Bioanalysis
  1. 9.1 Introduction
  2. 9.2 Plasma Microsampling Considerations
  3. 9.3 Dried Blood (Matrix) Spot (DBS) Considerations
  4. 9.4 Volumetric Absorptive Microsampling (VAMS)
  5. 9.5 Emerging Techniques
  6. 9.6 Summary
  7. Acknowledgements
  8. References
10. 10 Nanomaterials for Sample Preparation in LC‐MS Bioanalysis
  1. 10.1 Introduction
  2. 10.2 Carbon Nanomaterials
  3. 10.3 Metallic NPs
  4. 10.4 Nanoporous Materials
  5. 10.5 Future Perspectives
  6. Acknowledgements
  7. References
11. 11 Sample Preparation via Molecularly Imprinted Polymers (MIPs) in LC‐MS Bioanalysis
  1. 11.1 Introduction
  2. 11.2 Preparation of MIPs
  3. 11.3 MIPs for Sample Preparation in Bioanalysis
  4. 11.4 Fragment Imprinting
  5. 11.5 Summary
  6. References
12. 12 Stir‐bar Sorptive Extraction for Sample Preparation in LC‐MS Bioanalysis
  1. 12.1 Introduction
  2. 12.2 SBSE Principle
  3. 12.3 SBSE Steps
  4. 12.4 Derivatization
  5. 12.5 Coating Materials
  6. 12.6 Applications
  7. 12.7 Summary
  8. References
13. 13 Monolithic Spin Column Extraction in LC‐MS Bioanalysis
  1. 13.1 Introduction
  2. 13.2 History of Monoliths
  3. 13.3 The Use of Monolith as Sorbent in Solid‐Phase Extraction
  4. 13.4 Monolithic Spin Column for Sample Preparation
  5. References
14. 14 Aptamer‐based Sample Preparation in LC‐MS Bioanalysis
  1. 14.1 Introduction
  2. 14.2 Aptamer‐based Sample Preparation
  3. 14.3 Representative Protocols
  4. 14.4 Summary
  5. Acknowledgements
  6. References
15. 15 Sample Extraction via Electromembrane in LC‐MS Bioanalysis
  1. 15.1 Introduction
  2. 15.2 Factors Affecting the Extraction Efficiency of EME
  3. 15.3 Recent Developments in EME
  4. 15.4 Bioanalytical Applications
  5. 15.5 Summary
  6. References
Part II: Matrix‐specific Sample Preparation Techniques in LC‐MS Bioanalysis
1. 16 Tissue Sample Preparation in LC‐MS Bioanalysis
  1. 16.1 Introduction
  2. 16.2 Selection of Homogenization Method
  3. 16.3 Common Protocols
  4. 16.4 Protocols for Special Tissue Sample Preparation
  5. 16.5 Challenges Associated with Tissue Homogenization
  6. 16.6 Summary
  7. References
2. 17 Sample Preparation for LC‐MS Bioanalysis of Peripheral Blood Mononuclear Cells
  1. 17.1 Introduction
  2. 17.2 Peripheral Blood Mononuclear Cells (PBMCs)
  3. 17.3 Sample Preparation Workflow for LC‐MS Bioanalysis of PBMC Samples
  4. 17.4 Representative Protocols
  5. 17.5 Summary
  6. References
3. 18 Sample Preparation for LC‐MS Bioanalysis of Urine, Cerebrospinal Fluid, Synovial Fluid, Sweat, Tears, and Aqueous Humor Samples
  1. 18.1 Introduction
  2. 18.2 Sample Preparation Methods for Urine
  3. 18.3 Sample Preparation Methods for Cerebrospinal Fluid
  4. 18.4 Sample Preparation Methods for Synovial Fluid
  5. 18.5 Sample Preparation Methods for Sweat
  6. 18.6 Sample Preparation Methods for Tears
  7. 18.7 Sample Preparation Methods for Aqueous Humor
  8. 18.8 Summary
  9. References
4. 19 Sample Preparation for LC‐MS Bioanalysis of Liposomal Samples
  1. 19.1 Introduction
  2. 19.2 Major Types of Sample Extraction Techniques for Liposomal Samples
  3. 19.3 Key Considerations in Sample Preparation for Liposomal Samples
  4. 19.4 Typical Protocols
  5. 19.5 Summary
  6. References
Part III: Sample Preparation Techniques for LC‐MS Bioanalysis of Challenging Molecules
1. 20 Key Pre‐analytical Considerations in LC‐MS Bioanalysis
  1. 20.1 Introduction
  2. 20.2 The Pre‐analytical Phase
  3. 20.3 Bioanalytical Evaluation‐planning
  4. 20.4 Common Pre‐analytical Issues in LC‐MS Bioanalysis
  5. 20.5 Summary
  6. References
2. 21 Derivatization in Sample Preparation for LC‐MS Bioanalysis
  1. 21.1 Introduction
  2. 21.2 Derivatization Strategies
  3. 21.3 Key Considerations for Derivatization
  4. 21.4 Application of Derivatization for Quantitative LC‐MS Bioanalysis
  5. 21.5 Summary
  6. References
3. 22 Sample Preparation for LC‐MS Bioanalysis of Lipids
  1. 22.1 Introduction
  2. 22.2 Sample Preparation for LC‐MS Bioanalysis of Lipids
  3. 22.3 Case Studies of LC‐MS Bioanalysis of Lipids
  4. 22.4 Summary
  5. References
4. 23 Sample Preparation for LC‐MS Bioanalysis of Peptides
  1. 23.1 Introduction
  2. 23.2 Properties of Peptides and Sample Pretreatment
  3. 23.3 Sample Preparation Strategies
  4. 23.4 Conclusions
  5. Acknowledgements
  6. References
5. 24 Sample Preparation for LC‐MS Bioanalysis of Proteins
  1. 24.1 Introduction
  2. 24.2 Intact Versus Digested Protein Analysis
  3. 24.3 Enzymatic Digestion
  4. 24.4 Protein Depletion
  5. 24.5 Protein Extraction (Before Digestion)
  6. 24.6 Peptide Extraction (After Digestion)
  7. 24.7 Combined Protein and Peptide Extraction
  8. 24.8 Summary
  9. References
6. 25 Sample Preparation for LC‐MS Bioanalysis of Oligonucleotides
  1. 25.1 Introduction
  2. 25.2 Properties of Oligonucleotides and Associated Challenges in LC‐MS Bioanalysis
  3. 25.3 Classes of Oligonucleotides
  4. 25.4 Major Types of Sample Extraction Techniques
  5. 25.5 Key Considerations in Sample Preparation for LC‐MS Bioanalysis of Oligonucleotides
  6. 25.6 Representative Protocols
  7. 25.7 Summary
  8. References
7. 26 Sample Preparation for LC‐MS Bioanalysis of Antibody–Drug Conjugates
  1. 26.1 Introduction
  2. 26.2 Properties of ADC and Challenges for Sample Preparation
  3. 26.3 Sample Preparation Methods and Common Protocols
  4. 26.4 Future Perspective
  5. Acknowledgements
  6. References
Index
End User License Agreement

List of Tables

Chapter 1
1. Table 1.1 Commercially available protein precipitation plate/tubes.
2. Table 1.2 Commonly used organic solvents in LLE and their physicochemical...
Chapter 2
1. Table 2.1 Summary of extraction mechanisms and representative applica...
Chapter 3
1. Table 3.1 Advantages and disadvantages of (rapid) equilibrium dialysis (ED) for ...
2. Table 3.2 Advantages and disadvantages of ultrafiltration for sample preparation...
3. Table 3.3 Advantages and disadvantages of ultracentrifugation for sample prepara...
4. Table 3.4 Comparison of the advantages and disadvantages of three methods used f...
Chapter 4
1. Table 4.1 Summary of sample preparation strategies involved in monito...
Chapter 5
1. Table 5.1 Salting‐out assisted liquid–liquid extraction procedures for bioanalys...
Chapter 6
1. Table 6.1 Current applications involving SLE related to bioanalysis.
2. Table 6.2 Extraction recovery of 10 representative compounds under various extra...
Chapter 7
1. Table 7.1 Binding, washing, and elution buffers commonly used for immunocapture.
2. Table 7.2 Affinity of protein A and protein G to IgG subclass from different spe...
3. Table 7.3 A comparison of immunoglobulin binding proteins.
Chapter 8
1. Table 8.1 Bioanalytical methods for analysis of drugs and/or metaboli...
2. Table 8.2 Advantages, disadvantages, and trends of liquid‐phase microextr...
Chapter 9
1. Table 9.1 Effect of the different technique used to derive plasma for...
2. Table 9.2 Plasma concentrations of six over‐the‐counter drugs measure...
3. Table 9.3 Validation statistics for a GSK proprietary compound extrac...
Chapter 10
1. Table 10.1 A summary of characteristics of the different sample treatments using...
2. Table 10.2 Number of steps of the different sample treatments using nanomaterial...
3. Table 10.3 General advantages and disadvantages of the different types of nanoma...
Chapter 11
1. Table 11.1 Examples of MISPE in pharmaceutical analysis and bioanalys...
Chapter 12
1. Table 12.1 Examples of SBSE’s applications in bioanalysis.
Chapter 13
1. Table 13.1 Physicochemical properties of SPE columns.
2. Table 13.2 Physicochemical properties of commercial MonoSpin columns.
3. Table 13.3 Representative applications of MonoSpin® extraction in LC‐MS bioanaly...
Chapter 16
1. Table 16.1 Animal organ weight.
2. Table 16.2 Commonly used apparatus for tissue homogenization.
3. Table 16.3 Commonly used agents/enzymes for chemical or enzyme digest...
4. Table 16.4 Bead size and material selection for tissue interruption. ...
5. Table 16.5 Vial selection for beads beater tissue homogenization.
6. Table 16.6 Common parameters for beads beater homogenization (example...
7. Table 16.7 Homogenization of tissue for the analysis of labile analyt...
Chapter 18
1. Table 18.1 An example of urine sample preparation procedure using direct ...
2. Table 18.2 An example of urine sample preparation procedure using LLE....
3. Table 18.3 An example of urine sample preparation procedure using oasis M...
4. Table 18.4 An example of cerebrospinal fluid sample preparation procedure...
5. Table 18.5 An example of CSF sample preparation procedure using direct di...
6. Table 18.6 An example of synovial fluid sample preparation procedure usin...
7. Table 18.7 An example of synovial fluid sample preparation procedure usin...
8. Table 18.8 Sweat sample preparation procedure using direct dilution and f...
9. Table 18.9 Sweat sample preparation procedure using SPE with Micro SpinCo...
10. Table 18.10 Examples of tears sample preparation procedure using direct d...
11. Table 18.11 An example of tears sample preparation procedure using SPE....
12. Table 18.12 A typical aqueous humor sample preparation procedure using pr...
13. Table 18.13 An example of aqueous humor sample preparation procedure for ...
Chapter 20
1. Table 20.1 Proposed study design.
2. Table 20.2 Assay technical requirements.
3. Table 20.3 Whole blood sample collection/handling evaluation procedures...
Chapter 21
1. Table 21.1 Applications of various derivatization strategies.
Chapter 23
1. Table 23.1 Comparison of different sample preparation strategies for ...

List of Illustrations

Chapter 2
1. Figure 2.1 A schematic representation of online extraction LC‐MS/MS system with...
2. Figure 2.2 A schematic representation of online extraction LC‐MS/MS system with...
Chapter 3
1. Figure 3.1 Schematic representation of the equilibrium dialysis methodology.
2. Figure 3.2 Rapid equilibrium dialysis (RED) device. Each insert is comprised of...
3. Figure 3.3 Schematic representation of the ultrafiltration methodology.
4. Figure 3.4 Schematic representation of the ultracentrifugation methodology.
Chapter 4
1. Figure 4.1 Frameworks for common phospholipids found in membranes and plasma.
2. Figure 4.2 (a) (A) LC/MS/MS chromatograms of 250 μg ml⁻¹ phosphatidylchol...
3. Figure 4.3 In‐source CID spectra for GPChos at 90 V cone voltage on Quattro Mic...
4. Figure 4.4 TICs of MRM transitions for five phospholipids remaining in final ex...
5. Figure 4.5 The UHPLC‐MS/MS chromatograms for matrix (sturgeon) samples spiked w...
6. Figure 4.6 LC‐MS/MS separation of tamoxifen and its metabolites using steady‐st...
Chapter 5
1. Figure 5.1 Schematic diagram of the SALLE procedure.
Chapter 6
1. Figure 6.1 Procedure for supported liquid extraction.
Chapter 7
1. Figure 7.1 Summary of a typical immunocapture procedure.
2. Figure 7.2 Examples of different capture reagents.
3. Figure 7.3 Workflows of typical immunocapture formats. Protein (a), peptide (b)...
4. Figure 7.4 Evaluation of immunocapture recovery.
Chapter 8
1. Figure 8.1 Classification of the main microextraction techniques.
2. Figure 8.2 Main principles of solid‐phase microextraction (SPME) techniques: (a...
3. Figure 8.3 Main principles of liquid‐phase microextraction (LPME) techniques: (...
Chapter 9
1. Figure 9.1 Illustration of Drummond Capillary Device for plasma collection and ...
2. Figure 9.2 Statistical comparisons of air and positive displacement pipettes fo...
3. Figure 9.3 Illustration of MITRA Device for storage and collection of dried blo...
4. Figure 9.4 Illustration of MITRA Clamshell Device for storage and shipment of d...
Chapter 10
1. Figure 10.1 Basic principles of the main extraction techniques used with nanoma...
2. Figure 10.2 Extraction with MIPs: (a) preparation and (b) principle of MIPs for...
Chapter 11
1. Figure 11.1 Principle of molecular imprinting.
2. Figure 11.2 Single ion monitoring chromatograms of BPA, BPA‐¹³C₁₂, and BPA‐d₁₆ ...
3. Figure 11.3 Molecularly imprinted solid‐phase extraction (MISPE) procedure.
4. Figure 11.4 Experimental configuration of the online two‐step SPE‐LC procedure ...
5. Figure 11.5 Schematic of preparation of molecularly imprinted microSPE device.
Chapter 12
1. Figure 12.1 Diagram summarizing the most used methods for trace analysis of com...
2. Figure 12.2 The increase of β influences the theoretical efficiency of SBSE (PD...
3. Figure 12.3 Diagram summarizing the SBSE’s operating modes.
4. Figure 12.4 Illustration of derivatization modes. (a) In situ derivatization, (...
5. Figure 12.5 The structure of PDMS polymeric phase which has a glass transition ...
Chapter 13
1. Figure 13.1 Photograph of MonoSpin column (a), and electromicrograph of the dis...
2. Figure 13.2 General extraction procedure using MonoSpin columns.
3. Figure 13.3 Representative chromatograms of β‐blockers and calcium blockers obt...
Chapter 14
1. Figure 14.1 Typical schemes of the preparation of aptamer‐based affinity column...
2. Figure 14.2 Typical schemes of the preparation of aptamer‐immobilized magnetic ...
3. Figure 14.3 Scheme of the fabrication process and application of electrospun en...
Chapter 15
1. Figure 15.1 Typical electromembrane extraction setups for the extraction of aci...
2. Figure 15.2 Schematic illustration of on‐chip EME.
3. Figure 15.3 Schematic illustration for drop‐to‐drop EME.
Chapter 16
1. Figure 16.1 Response of test compound A in different tissues after FAF ultrason...
2. Figure 16.2 Average concentration of desipramine (a) and fluoxetine (b) in rat ...
3. Figure 16.3 Microscopic pictures of homogenate solution of mouse heart tissue. ...
Chapter 17
1. Figure 17.1 Illustration of blood separation for peripheral blood mononuclear c...
2. Figure 17.2 Illustration of blood separation for peripheral blood mononuclear c...
Chapter 18
1. Figure 18.1 Generic SPE procedures for biological sample preparation. MCX, mixe...
2. Figure 18.2 (a) Microduct^® Sweat Collection System; (b) Microduct Sweat Co...
3. Figure 18.3 Schirmer’s tear test strips.
Chapter 19
1. Figure 19.1 Different fractions of the drug in biological samples after adminis...
2. Figure 19.2 Time course of released (nonencapsulated) doxorubicin (DXR) and lip...
3. Figure 19.3 Solid‐phase extraction procedure for measurement of encapsulated an...
Chapter 20
1. Figure 20.1 The work flow of pertinent planning in the pre‐analytical phase bef...
Chapter 21
1. Figure 21.1 General mechanism of derivatization reactions.
2. Figure 21.2 Chemical structures of typical derivatization reagents for detectio...
3. Figure 21.3 Metabolic pathway of prasugrel (Rehmel et al. 2006).
4. Figure 21.4 Derivatization reaction of the active metabolite of prasugrel (R‐13...
5. Figure 21.5 Step‐by‐step procedure of derivatization strategy for minodronic ac...
Chapter 22
1. Figure 22.1 Classes of lipids.
2. Figure 22.2 ECAPCI/MS/HRMS of 15‐HETE‐PFB. The low‐energy electrons generated f...
3. Figure 22.3 Typical LC‐ECAPCI/MS/HRMS chromatograms of HETEs as PFB derivatives...
Chapter 23
1. Figure 23.1 General overview of sample preparation (including sample pretreatme...
Chapter 24
1. Figure 24.1 Schematic representation of the different components of sample prep...
2. Figure 24.2 LC‐MS/MS chromatograms for the surrogate peptide of 2.0 ng ml⁻¹...
3. Figure 24.3 Schematic representation of the removal of albumin from plasma by t...
4. Figure 24.4 Schematic representation of the immunocapture of PTH from human ser...
5. Figure 24.5 LC‐MS/MS chromatograms for the signature peptide of α1‐antichymotry...
6. Figure 24.6 Schematic representation of the combination of off‐line protein imm...
Chapter 25
1. Figure 25.1 The structure of oligonucleotide.
2. Figure 25.2 2′‐Endo and 3′‐endo conformations of sugar.
3. Figure 25.3 Schematic of phenol/chloroform LLE.
4. Figure 25.4 Oligonucleotide isolation by proteinase K digestion.
5. Figure 25.5 Solid‐phase extraction.
6. Figure 25.6 Ion‐exchange magnetic bead extraction.
7. Figure 25.7 Immunoaffinity capture approaches.
Chapter 26
1. Figure 26.1 Workflow depicting various sample preparation methods for quantitat...
2. Figure 26.2 Schematic illustration of sample preparation workflows for conjugat...
3. Figure 26.3 Workflow depicting sample preparation methods for conjugated antibo...
4. Figure 26.4 Workflow depicting sample preparation methods for total antibody qu...
5. Figure 26.5 Schematic illustration of sample preparation workflows for DAR anal...

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Library of Congress Cataloging‐in‐Publication Data

Names: Li, Wenkui, 1964– editor. | Jian, Wenying, editor. | Fu, Yunlin, 1980– editor.
Title: Sample preparation in LC‐MS bioanalysis / edited by Wenkui Li, Wenying Jian, Yunlin Fu.
Other titles: Sample preparation in liquid chromatography‐mass spectrometry bioanalysis
Description: Hoboken, NJ : Wiley, [2019] | Series: Wiley series on pharmaceutical science and biotechnology | Includes bibliographical references. |
Identifiers: LCCN 2018046969 (print) | LCCN 2018055539 (ebook) | ISBN 9781119274308 (Adobe PDF) | ISBN 9781119274322 (ePub) | ISBN 9781119274292 (hardcover)
Subjects: LCSH: Liquid chromatography. | Mass spectrometry. | Biotechnology.
Classification: LCC QD79.C454 (ebook) | LCC QD79.C454 S275 2019 (print) | DDC 543/.84–dc23
LC record available at https://lccn.loc.gov/2018046969

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List of Contributors

Gilberto Alves, PhD
CICS‐UBI – Health Sciences Research Centre
University of Beira Interior
Covilhã
Portugal

Miguel Ángel Bello‐López, PhD
Department of Analytical Chemistry
Universidad de Sevilla
Sevilla
Spain

Matthew Barfield, PhD
Research and Development
GlaxoSmithKline Pharmaceuticals
Ware
UK

Michael G. Bartlett, PhD
Department of Pharmaceutical and Biomedical Sciences
University of Georgia
Athens, GA
USA

Babak Basiri, PhD
Department of Pharmaceutical and Biomedical Sciences
University of Georgia
Athens, GA
USA

Ian A. Blair, PhD
Department of Systems Pharmacology and Translational Therapeutics
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA
USA

Chester L. Bowen, MS
Research and Development
GlaxoSmithKline Pharmaceuticals
Collegeville, PA
USA

Stacy Brown, PhD
Department of Pharmaceutical Sciences
Gatton College of Pharmacy at East Tennessee State University
Johnson City, TN
USA

Pilar Campíns‐Falcó, PhD
Química Analítica
Universitat de València
Burjassot
Spain

Jennifer Carmical, PharmD
Department of Pharmaceutical Sciences
Gatton College of Pharmacy at East Tennessee State University
Johnson City, TN
USA

Zhongzhe Cheng, PhD
School of Pharmacy
Weifang Medical University
Weifang, Shandong
China

Theo de Boer, PhD
LC‐MS Bioanalysis
Ardena Bioanalytical Laboratory (ABL)
Assen
The Netherlands

Myriam Díaz‐Álvarez, MSc
Department of Environment
Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA)
Madrid
Spain

Fuyou Du, PhD
Department of Applied Chemistry
Guilin University of Technology
Guilin, Guangxi
China

Amílcar Falcão, PhD
Laboratory of Pharmacology
Faculty of Pharmacy
University of Coimbra
Coimbra
Portugal

Rut Fernández‐Torres, PhD
Department of Analytical Chemistry
Universidad de Sevilla
Sevilla
Spain

Ana Fortuna, PhD
Laboratory of Pharmacology
Faculty of Pharmacy
University of Coimbra
Coimbra
Portugal

Yunlin Fu, MS
Pharmacokinetic Sciences
Novartis Institutes for BioMedical Research
East Hanover, NJ
USA

Hong Gao, PhD
Drug Metabolism & PharmacokineticsVertex Pharmaceuticals
Boston, MA
USA

Rodrigo A. González‐Fuenzalida, PhD
Química Analítica
Universitat de València
Burjassot
Spain

Rosa Herráez‐Hernández, PhD
Química Analítica
Universitat de València
Burjassot
Spain

Bruce J. Hidy, BSc
R&D, PPD
Richmond, VA
USA

Samuel Hofbauer, BS
Department of Systems Pharmacology and Translational Therapeutics
University of Pennsylvania
Philadelphia, PA
USA

Mike (Qingtao) Huang, PhD
Clinical Pharmacology
Akros Pharma Inc.
Princeton, NJ
USA

Rand G. Jenkins, BSc (retired)
PPD
Mechanicsville, VA
USA

Allena J. Ji, PhD, NRCC, DABCC
Biomarkers & Clinical Bioanalyses‐Boston, Sanofi
Framingham, MA
USA

Wenying Jian, PhD
Janssen Research & Development, LLC
Spring House, PA
USA

Hongliang Jiang, PhD
Tongji School of Pharmacy
Huazhong University of Science and Technology
Wuhan, Hubei
China

Neus Jornet‐Martinez, PhD
Química Analítica
Universitat de València
Burjassot
Spain

Maria Kechagia, MSc
Chemistry Department
Aristotle University of Thessaloniki
Thessaloniki
Greece

Jaeah Kim, PhD
Department of Pharmaceutical and Biomedical Sciences
University of Georgia
Athens, GA
USA

Maria Kissoudi, MSc
Chemistry Department
Aristotle University of Thessaloniki
Thessaloniki
Greece

Fumin Li, PhD
R&D, PPD
Middleton, WI
USA

Ning Li, PhD
Department of Pharmaceutical Analysis
School of Pharmacy
Shenyang Pharmaceutical University
Shenyang, Liaoning
China

Wenkui Li, PhD
Pharmacokinetic Sciences
Novartis Institutes for BioMedical Research
East Hanover, NJ
USA

Ang Liu, PhD
Bioanalytical Sciences
Translational Medicine
Bristol‐Myers Squibb
Princeton, NJ
USA

Rao N.V.S. Mamidi, PhD, DABT
Janssen Research & Development, LLC.
Raritan, NJ
USA

Yan Mao, PhD
Drug Metabolism & Pharmacokinetics
Boehringer Ingelheim Pharmaceuticals, Inc.
Ridgefield, CT
USA

Antonio Martín‐Esteban, PhD
Department of Environment
Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA)
Madrid
Spain

Henri Meijering, MSc
LC‐MS Bioanalysis
Ardena Bioanalytical Laboratory (ABL)
Assen
The Netherlands

Clementina Mesaros, PhD
Department of Systems Pharmacology and Translational Therapeutics
University of Pennsylvania
Philadelphia, PA
USA

Akira Namera, PhD
Department of Forensic Medicine
Graduate School of Biomedical and Health Sciences
Hiroshima University
Hiroshima
Japan

Ragu Ramanathan, PhD
Medicine Design – ADME Sciences, Pfizer, Inc
Groton, CT
USA

María Ramos‐Payán, PhD
Department of Analytical Chemistry
Universidad de Sevilla
Sevilla
Spain

Márcio Rodrigues, PhD
CICS‐UBI – Health Sciences Research Centre
University of Beira Interior
Covilhã
Portugal

Guihua Ruan, PhD
Department of Applied Chemistry
Guilin University of Technology
Guilin, Guangxi
China

Takeshi Saito, PhD
Department of Emergency and Critical Care Medicine
Tokai University School of Medicine
Isehara
Japan

Ashkan Salamatipour, BS
Department of Systems Pharmacology and Translational Therapeutics
University of Pennsylvania
Philadelphia, PA
USA

Victoria F. Samanidou, PhD
Chemistry Department
Aristotle University of Thessaloniki
Thessaloniki
Greece

Nico van de Merbel, PhD
PRA Health Sciences
Assen
The Netherlands

Cong Wei, PhD
Drug Metabolism & Pharmacokinetics, Vertex Pharmaceuticals
Boston, MA
USA

Zongyu Wei, MS
Department of Applied Chemistry
Guilin University of Technology
Guilin, Guangxi
China

Naidong Weng, PhD
Janssen Research & Development, LLC.
Spring House, PA
USA

John Williams, PhD
Drug Metabolism & Pharmacokinetics Vertex Pharmaceuticals
Boston, MAUSA

Xin Xiong, MS
Department of Pharmacy
Peking University Third Hospital
Beijing
China

Long Yuan, PhD
Bioanalytical Sciences
Bristol‐Myers Squibb
Princeton, NJ
USA

Qiulian Zeng, MS
Department of Applied Chemistry
Guilin University of Technology
Guilin, Guangxi
China

Jun Zhang, PhD
Dynamega LLC
Lake Forest, IL
USA

Dafang Zhong, PhD
Shanghai Institute of Materia Medica
Chinese Academy of Sciences
Shanghai
China

Yunting Zhu, PhD
Shanghai Institute of Materia Medica
Chinese Academy of Sciences
Shanghai
China

Preface

Sample preparation is a pivotal part of the integral LC‐MS bioanalysis, which has been heavily employed in the determination of drugs, drug metabolites, biomarkers, and other molecules of interest in various biological matrices (e.g. fluids or tissues) for decades. It has been playing an important role in a variety of human healthcare studies, ranging from drug discovery and development, therapeutic drug monitoring, to biomarker analysis. While highly sophisticated LC‐MS systems with better sensitivity and higher bioanalytical throughput have been continuously introduced, challenges that remain unchanged are the sample preparation prior to LC‐MS quantitation, for which data quality has direct impact on study conclusion.

The purpose of sample preparation is not only to make the analyte(s) of interest available in sample extracts at an appropriate concentration for MS detection but also to remove interfering matrix elements (e.g. phospholipids and salts) that, if not addressed properly, can alter MS response (e.g. signal suppression). In quantitative LC‐MS bioanalysis, clean sample extracts means: (i) better chromatography, (ii) lower limit of quantification, (iii) decreased assay variability (due to reduced matrix effects), (iv) less chance of false‐positive/negative results, (v) longer column lifetime, (vi) less instrument downtime, and (vii) minimized costs in manpower and equipment maintenance, etc. In practice, the best sample preparation strategies should always be considered, evaluated, and implemented whenever possible in developing a robust quantitative LC‐MS bioanalytical method.

As a companion for the previously published Handbook of LC‐MS Bioanalysis: Best Practice, Experimental Protocols and Regulations (Li, Zhang, and Tse, 2013, Wiley), the current book is to provide a timely and comprehensive update along with representative experimental protocols on all important sample preparation techniques for quantitative LC‐MS bioanalysis of small and large molecules. The 26 chapters of the book are divided into three parts. The first part of the book is focused on not only the basic but also the contemporary sample preparation techniques in LC‐MS bioanalysis. These include Protein Precipitation, Liquid–Liquid Extraction, and Solid‐Phase Extraction (Chapter 1), Online Extraction and Column Switching (Chapter 2), Equilibrium Dialysis, Ultracentrifugation, and Ultrafiltration (Chapter 3), Phospholipid Depletion (Chapter 4), Salting‐out Assisted Liquid–Liquid Extraction (SALLE) (Chapter 5), Supported Liquid Extraction (SLE) (Chapter 6), Immunocapture (Chapter 7), Microextraction (Chapter 8), Microsampling (Chapter 9), Extraction via Nanomaterials (Chapter 10), Extraction via Molecularly Imprinted Polymers (MIP) (Chapter 11), Stir‐bar Sorptive Extraction (Chapter 12), Monolithic Spin Column Extraction (Chapter 13), Aptamer‐based Sample Preparation (Chapter 14), and Sample Extraction via Electromembranes (Chapter 15).

In Part II, the current sample preparation techniques for LC‐MS bioanalysis of biological sample matrices other than common whole blood, plasma, or serum are discussed in detail along with experimental protocols. These matrices include but are not limited to Tissues, Hair, Nail, Skins, and Bones (Chapter 16), Peripheral Blood Mononuclear Cells (Chapter 17), Urine, Cerebrospinal Fluid, Synovial Fluid, Sweat, Tears, and Aqueous Humor (Chapter 18), and Liposomal Samples (Chapter 19).

Part III of the book is focused on sample preparation for LC‐MS bioanalysis of challenging molecules. This part starts with some Key Pre‐analytical Considerations in Quantitative LC‐MS Bioanalysis (Chapter 20), which is followed by Derivatization strategies for enhancing assay sensitivities in quantitative LC‐MS bioanalysis of molecules with poor ionization efficiency (Chapter 21). Sample preparation for quantitative LC‐MS bioanalysis of Lipids is captured in Chapter 22. In Chapter 23, detailed instructions and associated stepwise protocols are provided for LC‐MS bioanalysis of peptides. Expanding from peptides, detailed instructions of sample preparation for LC‐MS bioanalysis of Proteins, Oligonucleotides, and Antibody–drug Conjugates (ADCs) are captured in Chapters 24, 25, and 26, respectively.

Our purpose in committing to this project was to provide scientists in industry, academia, and regulatory agencies with all “practical tricks” in extracting various analyte(s) of interest from biological samples for LC‐MS quantification according to the current health authority regulations and industry practices. In this book we are confident that we have accomplished our goal. The book represents a major undertaking which would not have been possible without the contributions of all the authors and the support of their families. We also wish to thank the terrific editorial staff at John Wiley & Sons and give a special acknowledgment to Michael Leventhal, Managing Editor; Vishnu Narayanan, Project Editor; Beryl Mesiadhas, Project Manager; S. Grace Paulin Jeeva, Production Editor; and Robert Esposito, Associate Publisher, at John Wiley & Sons, for their premier support of this project.

Wenkui Li, PhD
Wenying Jian, PhD
Yunlin Fu, MS

List of Abbreviations

2D: two‐dimensional
3NPH: 3‐nitrophenylhydrazine
5‐FU: 5‐fluorouracil
5‐HETE: 5‐hydroxyeicosatetraenoic acid
AA: acrylamide
AA: alendronic acid
AAC: α1‐antichymotrypsin
ACE: angiotensin I converting enzyme
ACE: automatic cartridge exchange
ACN: acetonitrile
ADA: anti‐drug antibody
ADC: antibody–drug conjugate
ADME: absorption, distribution, metabolism, and excretion
ADP: adenosine diphosphate
ADS: alkyl‐diol‐silica
AFA: adaptive focused acoustics
AFMC: aptamer‐functionalized monolithic column
AFMPC: aptamer‐functionalized material‐packed column
AFM: aptamer‐functionalized material
AFOTCC: aptamer‐functionalized open tubular capillary column
AFSC: aptamer‐functionalized spin column
AG: 2‐arachidonoylglycerol
AGP: acid glycoprotein
AIBN: azo(bis) isobutyronitrile
AML: acute myeloid leukemia
AMP: adenosine monophosphate
APA: anti‐peptide antibody
APCI: atmospheric pressure chemical ionization
Apt‐AC: aptamer‐based affinity column
Apt‐AuNR: aptamer‐functionalized gold nanorod
Apt‐MM: aptamer‐functionalized magnetic material
Apt‐MNP: aptamer‐functionalized magnetic nanoparticle
Apt‐PANCMA: aptamer‐functionalized poly(acrylonitrile‐co‐maleic acid)
Apt‐PP‐fiber: aptamer‐based‐polypropylene fiber
Apt‐SA‐SPE: aptamer‐based surface affinity solid‐phase extraction
Apt‐SBSE: aptamer‐functionalized stir‐bar sorptive extraction
Apt‐SPE: aptamer‐based solid‐phase extraction
Apt‐SPME: aptamer‐based solid‐phase microextraction
ATP: adenosine triphosphate
AUC: area under the curve
AuNP: gold nanoparticle
BAL: bronchoalveolar lavage
BEAD: bead extraction and acid dissociation
BEH: bridged ethylene hybrid
BLQ: below limit of quantification
BNP: B‐type natriuretic peptide
BP: bisphosphonate
BP‐3: benzophenone‐3
BPA: bisphenol A
BSA: bovine serum albumin
BSL‐2: biosafety level‐2
BSTFA: N,O‐bis(trimethylsilyl)trifluoroacetamide
CAD: collision‐activated dissociation
Cape: capecitabine
CCSHLLE: counter current salting‐out homogenous liquid–liquid extraction
CDA: cytidine deaminase
CDI: carbonyl diimidazole
CDR: complementarity‐determining region
CE: capillary electrophoresis
CE: cholestryl oleate
CHAPS: 3‐([3‐cholamidopropyl]dimethylammonio)‐1‐propanesulfonate
CID: collision‐induced dissociation
CIP: chiral imprinted polymer
CNBF: 4‐chloro‐3,5‐dinitrobenzotrifloride
CNS: central nervous system
CNT‐PDMS: carbon nanotube–poly(dimethylsiloxane)
CNT: carbon nanotube
COXs: cyclooxygenases
CPT: cell preparation tube
CSF: cerebrospinal fluid
CV: coefficient of variation
CZE‐C⁴D: capillary zone electrophoresis with capacitively coupled contactless conductivity detection
D: distribution ratio
D2EHPA: di‐(2‐ethylhexyl)phosphoric acid
DAD: diode array detection
DADPA: diaminodipropylamine
DAG: diacylglycerol (1,3‐dilinoleoyl‐rac‐glycerol)
DAR: drug‐to‐antibody ratio
DBS: dried blood spot
DCM: dichloromethane
DEHP: di‐(2‐ethylhexyl) phosphate
DEME: dynamic electromembrane extraction
DEX: dextromethorphan
DI: direct immersion
DIC: diclofenac
DIEA: diisopropylethylamine
DI‐SDME: direct immersion single‐drop microextraction
DLLE: dispersive liquid–liquid extraction
DLLME: dispersive liquid–liquid microextraction
DMBA: dimethylbutylamine
DMF: N,N‐dimethylformamide
DMSO: dimethyl sulfoxide
DNS‐Cl: dansyl chloride
DOPA: dihydroxyphenylalanine
DOR: dextrorphan
DP IV: dipeptidyl peptidase IV
DPBS: Dulbecco’s phosphate‐buffered saline
DPX: disposable pipette extraction
DSEA: dansyl sulfonamide ethyl amine
D‐SPE: dispersive solid‐phase extraction
DTT: dithiothreitol
DVB: divinylbencene
DXR: doxorubicin
EA: ethyl acetate
EBF: European Bioanalytical Forum
ECAPCI: electro capture atmospheric pressure chemical ionization
ED: equilibrium dialysis
EDC·HCl: 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide hydrochloride
EDC/NHS: N‐(3‐dimethylamnopropyl)‐N‐ethylcarbodiimide hydrochloride/N‐hydroxysuccinimide
EDTA: ethylenediaminetetraacetic acid
EG: ethylene glycol
EGDMA: ethylene glycol dimethacrylate
EHS: ethylhexyl salicylate
ELISA: enzyme‐linked immunosorbent assay
EME: electromembrane extraction
EME‐DLLME: electromembrane extraction dispersive liquid–liquid microextraction
EME‐LDS‐USAEME: electromembrane extraction low‐density solvent‐based ultrasound‐assisted emulsification electromembrane microextraction
EM‐SPME: electromembrane‐surrounded solid‐phase microextraction
ENB: 1‐ethyl‐2‐nitrobenezene
EPR: enhanced permeation and retention
ESI: electrospray ionization
EtOH: ethanol
FA: fatty acid
FA: formic acid
FBAL: α‐fluoro‐β‐alanine
FBS: fetal bovine serum
Fc: fragment crystallizable region/constant region
FcRn: human neonatal Fc receptor
FDA: Food and Drug Administration
FLD: fluorescence detection
FLM: free liquid membrane
Fmoc‐Cl: 9‐florenylmethoxycarbonyl chloride
FNME: fiber‐packed needle microextraction
GAC: green analytical chemistry
GC: gas chromatography
GC‐FID: gas chromatography–flame ionization detection
GC‐MS: gas chromatography–mass spectrometry
GIP: glucose‐dependent insulintropic peptide
GLP‐1: glucagon‐like peptide‐1
GMA: glycidylmethacrylate
GnRH: gonadotropin‐releasing hormone
GPChos: glycerophosphatidylcholines
GPCs: glycerophosphatidylcholines
GPE: gum‐phase extraction
GPI: glycosylphosphatidylinositol
HETP: height equivalent to a theoretical plate
HFIP: 1,1,1,3,3,3‐hexafluoro‐isopropanol
HF‐LPME: hollow fiber liquid‐phase microextraction
HILIC: hydrophilic interaction liquid chromatography
HIV: human immunodeficiency virus
HMS: homosalate
HND‐G: high nitrogen‐doped graphene
HNE: human neutrophil elastase
HPIM: homemade polymer inclusion membrane
HPLC: high‐performance liquid chromatography
HRMS: high‐resolution mass spectrometry
HS: headspace
HSSBSE: headspace stir‐bar sorptive extraction
HS‐SDME: headspace single‐drop microextraction
HTLC: high‐turbulence liquid chromatography
IACUC: Institutional Animal Care and Use Committee
IAE: immunoaffinity extraction
IAM: iodoacetamide
IA‐SPE: immunoaffinity solid‐phase extraction
IC: immunocapture
iCAT: isotope‐coded affinity tag
ICP‐MS: inductively coupled plasma mass spectrometry
ID: internal diameter
IGF: insulin‐like growth factor
IgG: immunoglobulin G
IL‐21: interleukin‐21
IMAC: immobilized metal ion affinity chromatography
IPA: isopropanol
IS: internal standard
ISET: integrated selective enrichment target
IS‐MRM: in‐source multiple reaction monitoring
ISR: incurred sample reanalysis
ISTD: internal standard
ITMS: ion trap mass spectrometry
iTRAQ: isobaric tags for relative and absolute quantification
IT‐SPME: in‐tube solid‐phase microextraction
IUPAC: International Union of Pure and Applied Chemistry
IV: intravenous
IVT: in vitro transcription
IX‐SPE: ion exchange‐solid‐phase extraction
Kb/p: blood to plasma ratio
Ke/p: red blood cell partition coefficient
LBA: ligand‐binding assay
LC: liquid chromatography
LC‐MS: liquid chromatography–mass spectrometry
LC‐MS/MS: liquid chromatography–tandem mass spectrometry
LC‐UV/FL: liquid chromatography with ultraviolet/fluorescence detection
LD: liquid desorption
LGPChos: lysoglycerophosphocholines
LLE: liquid–liquid extraction
LLOQ: lower limit of quantification
LOXs: lipoxygenases
LPCs: lyso‐phosphatidylcholines
LPME: liquid‐phase microextraction
LSC: liquid scintillation counting
MA: methyacrylate, methyl acrylate
MA: minodronic acid
MAA: methacrylamide
MAA: methacrylic acid
mAb: monoclonal antibody
MADB: poly(methacrylic acid‐3‐sulfopropyl ester potassium salt‐co‐divinylbenzene)
MAG: monoacylglycerol (1‐stearyl‐rac‐l glycerol)
MALDI: matrix‐assisted laser desorption ionization
MAX: mixed‐mode anion exchange
MCV: mean cell volume
MCX: mixed‐mode cation exchange
MDA‐LDL: malondialdehyde‐modified low‐density lipoprotein
MDMA: 3,4‐methylenedioxy‐N‐methylamphetamine
MDS: myelodysplastic syndromes
MeOH: methanol
MEPS: microextraction by packed sorbent
MF: matrix factor
MI‐MSPE: molecularly imprinted micro‐solid‐phase extraction
MIPs: molecularly imprinted polymers
MISPE: molecularly imprinted solid‐phase extraction
MISPE‐DPE: molecularly imprinted solid‐phase extraction with differential pulsed elution
MISPE‐PE: molecularly imprinted solid‐phase extraction with pulsed elution
MIST: metabolites in safety testing
MIT: molecular imprinting technology
MLLE: micro‐liquid–liquid extraction
MMA: methylmalonic acid
MMAE: monomethyl auristatin E
MMST: monolithic molecularly imprinted polymer sol–gel packed tip
MNP: magnetic nanoparticle
MPB: 2‐bromo‐3′‐methoxyacetophenone
mPGES‐1: microsomal prostaglandin E synthase‐1
MPS: 3‐methacryloyloxypropyltrimethoxysilane
MRM: multiple reaction monitoring
mRNA: messenger RNA
MS: mass spectrometry
MS/MS: tandem mass spectrometry
MSP: magnetic supraparticle
MSPD: matrix solid‐phase dispersion
MSPE: magnetic solid‐phase extraction
MTBE: methyl tert‐butyl ether
MTBSTFA: N‐(tert‐butyldimethylsilyl)‐N‐methyl trifluoroacetamide
MW: molecular weights
MWCNT: multiwall carbon nanotube
MWCO: molecular weight cutoff
NAaPs: nucleic acid associated proteins
NAb: neutralizing antibody
NA: nucleic acid
NCEs: new chemical entities
NEM: N‐ethylmaleimide
NHS: N‐hydroxysuccinimide
NK: natural killer
NPOE: 2‐nitrophenyloctyl ether
NPPE: 2‐nitrophenyl pentyl ether
NPs: nanoparticles
NSB: nonspecific binding
NSE: neuron‐specific enolase
NTproBNP: N‐terminal pro‐B‐natriuretic peptide
OC: octocrylene
OD‐PABA: ethylhexyl dimethyl p‐aminobenzoate
ODS: octadecyl
OH‐PAH: monohydroxylated polycyclic aromatic hydrocarbon
OH‐PDMS: hydroxyl polydimethylsiloxane
OTT: open tubular trapping
OxLDL: oxidized low‐density lipoprotein
P: partition ratio
PA: phosphatidic acid
PA: polyacrylate
PA‐EG: poly(methyl methacrylate/ethyleneglycoldimethacrylate)
Pa‐EME: parallel electromembrane extraction
PALME: parallel artificial liquid membrane extraction
PANCMA: poly(acrylonitrile‐co‐maleic acid)
PAR: peak area ratio
PBD: pyrrolobenzodiazepine
PBMC: peripheral blood mononuclear cell
PBS: phosphate‐buffered saline
PBST: phosphate‐buffered saline with Tween‐20
PCA: perchloric acid
PCB: polychlorinated biphenyl
PCI: protein C inhibitor
PCs: phosphatidylcholines
PD: pharmacodynamics
PD: phospholipid depletion
PDMS: polydimethylsiloxane
PE: phosphoethanolamine
PEG: polyethylene glycol
PEME: pulsed electromembrane extraction
PEO: polyethylene oxide
PE: phosphatidylethanolamine
PFB: pentafluorobenzyl
PG: phosphatidylglycerol
PGs: prostaglandins
PHMB: 4‐(hydroxymercuri)benzoate
PI: phosphatidylinositol
PK: pharmacokinetics
PK/PD: pharmacokinetic/pharmacodynamic
PK/TK: pharmacokinetic/toxicokinetic
PKU: phenylketonuria
PLs: phospholipids
PMMA: pentamethylated minodronic acid
PMMA: poly(methyl methacrylate)
PMSF: phenylmethylsulfonyl fluoride
poly(GMA‐co‐EDMA): poly(glycidyl methacrylate‐coethylene dimethacrylate)
PP: polypropylene
PPB: plasma protein binding
PPESK: poly(phthalazine ether sulfone ketone)
PP‐fiber: porous polymer‐coated fiber
PPT: protein precipitation
PPY: polypyrrole
ProGRP: pro‐gastrin releasing peptide
PS: phosphatidylserine
PTFE: polytetrafluorethylene
PTV: programmable temperature vaporize
PU: polyurethane foams
PUFA: polyunsaturated fatty acids
QC: quality control
QTOF: quadropole time‐of‐flight
QuEChERS: quick, easy, cheap, effective, rugged, safe extraction method
RA: risedronic acid
RAM: restricted access material
RBC: red blood cell
REC: extraction recovery
RED: rapid equilibrium dialysis
rhTRAIL: recombinant human tumor necrosis factor‐related apoptosis‐inducing ligand
RISC: RNA‐induced silencing complex
ROS: reactive oxygen species
RP: reversed phase
RP‐SPE: reversed‐phase solid‐phase extraction
RPV: rilpivirine
SA‐EME: surfactant‐assisted electromembrane extraction
SALLE: salting‐out assisted liquid–liquid extraction
SAX: strong anion exchange
SBSE: stir‐bar sorptive extraction
SCAP: sample card and prep
SCIT: (+)‐(S)‐citalopram
SCX: strong cation exchange
SDCIT: (+)‐(S)‐desmethylcitalopram
SDDCIT: (+)‐(S)‐didesmethylcitalopram
SDF: stromal cell‐derived factor
SDME: single‐drop microextraction
SDS‐PAGE: sodium dodecyl sulphate–polyacrylamide gel electrophoresis
SDU: solvent delivery unit
sEGFR: soluble epidermal growth factor receptor
SELEX: systematic evolution of ligands by exponential enrichment
SF: synovial fluid
SHBG: sex hormone‐binding globulin
SIL: stable isotope labeled
SIL‐IS: stable isotopically labeled internal standard
SiNWA: silicon nanowire array
SISCAPA: stable isotope standards and capture by anti‐peptide antibodies
SLE: supported liquid extraction
SLM: supported liquid membrane
SM: sphingomyelin
SPDE: solid‐phase dynamic extraction
SPE: solid‐phase extraction
SPME: solid‐phase microextraction
SRM: selected reaction monitoring
SRM: single reaction monitoring
SSH: steroid sex hormone
SWCNT: single‐wall carbon nanotube
TAG: triacylglycerol (1,3‐dipalmitoyl,2oleoyl‐glycerol)
TAHS: p‐N,N,N‐trimethylammonioanilyl N′‐hydroxysuccinimidyl carbamate iodide
TBS: tris‐buffered saline
TCA: trichloroacetic acid
TCAFMF: thermally controlled aptamer‐functionalized microfluid
TCEP: tris(2‐carboxyethyl)phosphine
TD: thermal desorption
TD: toxicodynamic
TDU: thermal desorption unit
TEA: triethylamine
TEHP: tris(2‐ethylhexyl)phosphate
TEPA: tetraethylenepentamine
TFA: trifluoroacetic acid
TFC: turbulent flow chromatography
TFME: thin‐film microextraction
Tg: thyroglobulin
THCA: 11‐nor‐9‐carboxy‐Δ⁹‐tetrahydrocannabinol
THF: tetrahydrofuran
THU: tetrahydrouridine
Ti: titanium
TK: toxicokinetic
TK/TD: toxicokinetic/toxicodynamic
TLC: thin layer chromatography
TMMA: tetramethyl minodronic acid
TMS‐DAM: trimethylsilyldiazomethane
TNFα: tumor necrosis factor alpha
TRAIL: tumor necrosis factor‐related apoptosis‐inducing ligand
Tris: tri(hydroxymethyl)aminomethane
TSV‐DEME: two‐step voltage dual electromembrane extraction
TXB₂: thromboxane B₂
Tyr: tyrosine
UC: ultracentrifugation
UF: ultrafiltration
UHPLC: ultra‐high‐performance liquid chromatography
ULOQ: upper limit of quantitation
UPLC: ultra performance liquid chromatography
UV: ultraviolet
VAMS: volumetric absorptive microsampling
VIDB: vinylimidazole–divinylbenzene
VPy: vinylpyridine
WAX: weak anion exchange
WBC: white blood cell
WCX: weak cation exchange
Zr: zirconium
β‐NGF: beta‐nerve growth factor
γ‐MPTS: γ‐mercaptopropyltrimethoxysilane
μ‐EME: micro‐electromembrane extraction
μ‐SPE: micro‐SPE

WILEY SERIES ON PHARMACEUTICAL SCIENCE AND BIOTECHNOLOGY: PRACTICES, APPLICATIONS, AND METHODS

Sample Preparation in LC‐MS Bioanalysis

List of Contributors

Preface

List of Abbreviations

Part I
Current Sample Preparation Techniques in LC‐MS Bioanalysis