Sample Preparation in LC-MS Bioanalysis E-Book
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- Herausgeber: John Wiley & Sons
- Kategorie: Wissenschaft und neue Technologien
- Serie: Wiley Series on Pharmaceutical Science
- Sprache: Englisch
Revised and Expanded Handbook Provides Comprehensive Introduction and Complete Instruction for Sample Preparation in Vital Category of Bioanalysis Following in the footsteps of the previously published Handbook of LC-MS Bioanalysis, this book is a thorough and timely guide to all important sample preparation techniques used for quantitative Liquid Chromatography-Mass Spectrometry (LC-MS) bioanalysis of small and large molecules. LC-MS bioanalysis is a key element of pharmaceutical research and development, post-approval therapeutic drug monitoring, and many other studies used in human healthcare. While advances are continually being made in key aspects of LC-MS bioanalysis such as sensitivity and throughput, the value of research/study mentioned above is still heavily dependent on the availability of high-quality data, for which sample preparation plays the critical role. Thus, this text provides researchers in industry, academia, and regulatory agencies with detailed sample preparation techniques and step-by-step protocols on proper extraction of various analyte(s) of interest from biological samples for LC-MS quantification, in accordance with current health authority regulations and industry best practices. The three sections of the book with a total of 26 chapters cover topics that include: * Current basic sample preparation techniques (e.g., protein precipitation, liquid-liquid extraction, solid-phase extraction, salting-out assisted liquid-liquid extraction, ultracentrifugation and ultrafiltration, microsampling, sample extraction via electromembranes) * Sample preparation techniques for uncommon biological matrices (e.g., tissues, hair, skin, nails, bones, mononuclear cells, cerebrospinal fluid, aqueous humor) * Crucial aspects of LC-MS bioanalytical method development (e.g., pre-analytical considerations, derivation strategies, stability, non-specific binding) in addition to sample preparation techniques for challenging molecules (e.g., lipids, peptides, proteins, oligonucleotides, antibody-drug conjugates) Sample Preparation in LC-MS Bioanalysis will prove a practical and highly valuable addition to the reference shelves of scientists and related professionals in a variety of fields, including pharmaceutical and biomedical research, mass spectrometry, and analytical chemistry, as well as practitioners in clinical pharmacology, toxicology, and therapeutic drug monitoring.
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Table of Contents
Cover
List of Contributors
Preface
List of Abbreviations
Part I: Current Sample Preparation Techniques in LC‐MS Bioanalysis
1 Basic Sample Preparation Techniques in LC‐MS Bioanalysis
1.1 Introduction
1.2 Physicochemical Properties of Drugs and Their Metabolites
1.3 Pre‐analytical Variables of Analyte(s) of Interest in Biological Matrix
1.4 Most Commonly Used Sample Preparation Methods in LC‐MS Bioanalysis
References
2 Online Extraction and Column Switching Techniques in LC‐MS Bioanalysis
2.1 Introduction
2.2 System Configuration
2.3 Commonly Used Online Extraction Techniques
2.4 Considerations for Utilizing Online Extraction Techniques
2.5 Summary
References
3 Equilibrium Dialysis, Ultracentrifugation, and Ultrafiltration in LC‐MS Bioanalysis
3.1 Introduction
3.2 Challenges and Considerations
3.3 Experimental Procedures
3.4 Summary
References
4 Phospholipid Depletion Techniques in LC‐MS Bioanalysis
4.1 Introduction
4.2 Impact of Phospholipids on Bioanalytical Methods
4.3 Investigating Matrix Effects Associated with Phospholipids
4.4 Minimizing Matrix Effects Associated with Phospholipids
4.5 Removing Phospholipids Prior to LC‐MS Analysis
4.6 Example Methods that Demonstrate Successful Phospholipid Removal
4.7 Conclusions
Acknowledgement
References
5 Salting‐out Assisted Liquid–Liquid Extraction (SALLE) in LC‐MS Bioanalysis
5.1 Introduction
5.2 Considerations in Developing a SALLE Method
5.3 Combination of SALLE with Other Extraction Techniques
5.4 Matrix Effect in SALLE
5.5 Miniaturization and Automatization
5.6 Summary
References
6 Supported Liquid Extraction (SLE) in LC‐MS Bioanalysis
6.1 Introduction
6.2 Principle of SLE
6.3 Advantages and Limitation of SLE in Quantitative LC‐MS Bioanalysis
6.4 Key Consideration in Developing Robust SLE‐LC‐MS Bioanalytical Method
6.5 Representative Protocols
6.6 Summary
References
7 Immunocapture in LC‐MS Bioanalysis
7.1 Introduction
7.2 Experimental Workflow and Optimization
7.3 Considerations on the Selection of Capture Reagents and the Limitations
7.4 Platforms for Immunocapture
7.5 Internal Standard Selection
7.6 Performance Evaluation
7.7 Applications and Representative Protocols
7.8 Validation Criteria and Regulatory Considerations
7.9 Summary
References
8 Microextraction Techniques in LC‐MS Bioanalysis
8.1 Introduction
8.2 Solid‐Phase Microextraction
8.3 Liquid‐Phase Microextraction
8.4 Summary
Acknowledgements
References
9 Microsampling Applications with LC‐MS Bioanalysis
9.1 Introduction
9.2 Plasma Microsampling Considerations
9.3 Dried Blood (Matrix) Spot (DBS) Considerations
9.4 Volumetric Absorptive Microsampling (VAMS)
9.5 Emerging Techniques
9.6 Summary
Acknowledgements
References
10 Nanomaterials for Sample Preparation in LC‐MS Bioanalysis
10.1 Introduction
10.2 Carbon Nanomaterials
10.3 Metallic NPs
10.4 Nanoporous Materials
10.5 Future Perspectives
Acknowledgements
References
11 Sample Preparation via Molecularly Imprinted Polymers (MIPs) in LC‐MS Bioanalysis
11.1 Introduction
11.2 Preparation of MIPs
11.3 MIPs for Sample Preparation in Bioanalysis
11.4 Fragment Imprinting
11.5 Summary
References
12 Stir‐bar Sorptive Extraction for Sample Preparation in LC‐MS Bioanalysis
12.1 Introduction
12.2 SBSE Principle
12.3 SBSE Steps
12.4 Derivatization
12.5 Coating Materials
12.6 Applications
12.7 Summary
References
13 Monolithic Spin Column Extraction in LC‐MS Bioanalysis
13.1 Introduction
13.2 History of Monoliths
13.3 The Use of Monolith as Sorbent in Solid‐Phase Extraction
13.4 Monolithic Spin Column for Sample Preparation
References
14 Aptamer‐based Sample Preparation in LC‐MS Bioanalysis
14.1 Introduction
14.2 Aptamer‐based Sample Preparation
14.3 Representative Protocols
14.4 Summary
Acknowledgements
References
15 Sample Extraction via Electromembrane in LC‐MS Bioanalysis
15.1 Introduction
15.2 Factors Affecting the Extraction Efficiency of EME
15.3 Recent Developments in EME
15.4 Bioanalytical Applications
15.5 Summary
References
Part II: Matrix‐specific Sample Preparation Techniques in LC‐MS Bioanalysis
16 Tissue Sample Preparation in LC‐MS Bioanalysis
16.1 Introduction
16.2 Selection of Homogenization Method
16.3 Common Protocols
16.4 Protocols for Special Tissue Sample Preparation
16.5 Challenges Associated with Tissue Homogenization
16.6 Summary
References
17 Sample Preparation for LC‐MS Bioanalysis of Peripheral Blood Mononuclear Cells
17.1 Introduction
17.2 Peripheral Blood Mononuclear Cells (PBMCs)
17.3 Sample Preparation Workflow for LC‐MS Bioanalysis of PBMC Samples
17.4 Representative Protocols
17.5 Summary
References
18 Sample Preparation for LC‐MS Bioanalysis of Urine, Cerebrospinal Fluid, Synovial Fluid, Sweat, Tears, and Aqueous Humor Samples
18.1 Introduction
18.2 Sample Preparation Methods for Urine
18.3 Sample Preparation Methods for Cerebrospinal Fluid
18.4 Sample Preparation Methods for Synovial Fluid
18.5 Sample Preparation Methods for Sweat
18.6 Sample Preparation Methods for Tears
18.7 Sample Preparation Methods for Aqueous Humor
18.8 Summary
References
19 Sample Preparation for LC‐MS Bioanalysis of Liposomal Samples
19.1 Introduction
19.2 Major Types of Sample Extraction Techniques for Liposomal Samples
19.3 Key Considerations in Sample Preparation for Liposomal Samples
19.4 Typical Protocols
19.5 Summary
References
Part III: Sample Preparation Techniques for LC‐MS Bioanalysis of Challenging Molecules
20 Key Pre‐analytical Considerations in LC‐MS Bioanalysis
20.1 Introduction
20.2 The Pre‐analytical Phase
20.3 Bioanalytical Evaluation‐planning
20.4 Common Pre‐analytical Issues in LC‐MS Bioanalysis
20.5 Summary
References
21 Derivatization in Sample Preparation for LC‐MS Bioanalysis
21.1 Introduction
21.2 Derivatization Strategies
21.3 Key Considerations for Derivatization
21.4 Application of Derivatization for Quantitative LC‐MS Bioanalysis
21.5 Summary
References
22 Sample Preparation for LC‐MS Bioanalysis of Lipids
22.1 Introduction
22.2 Sample Preparation for LC‐MS Bioanalysis of Lipids
22.3 Case Studies of LC‐MS Bioanalysis of Lipids
22.4 Summary
References
23 Sample Preparation for LC‐MS Bioanalysis of Peptides
23.1 Introduction
23.2 Properties of Peptides and Sample Pretreatment
23.3 Sample Preparation Strategies
23.4 Conclusions
Acknowledgements
References
24 Sample Preparation for LC‐MS Bioanalysis of Proteins
24.1 Introduction
24.2 Intact Versus Digested Protein Analysis
24.3 Enzymatic Digestion
24.4 Protein Depletion
24.5 Protein Extraction (Before Digestion)
24.6 Peptide Extraction (After Digestion)
24.7 Combined Protein and Peptide Extraction
24.8 Summary
References
25 Sample Preparation for LC‐MS Bioanalysis of Oligonucleotides
25.1 Introduction
25.2 Properties of Oligonucleotides and Associated Challenges in LC‐MS Bioanalysis
25.3 Classes of Oligonucleotides
25.4 Major Types of Sample Extraction Techniques
25.5 Key Considerations in Sample Preparation for LC‐MS Bioanalysis of Oligonucleotides
25.6 Representative Protocols
25.7 Summary
References
26 Sample Preparation for LC‐MS Bioanalysis of Antibody–Drug Conjugates
26.1 Introduction
26.2 Properties of ADC and Challenges for Sample Preparation
26.3 Sample Preparation Methods and Common Protocols
26.4 Future Perspective
Acknowledgements
References
Index
End User License Agreement
List of Tables
Chapter 1
Table 1.1 Commercially available protein precipitation plate/tubes.
Table 1.2 Commonly used organic solvents in LLE and their physicochemical...
Chapter 2
Table 2.1 Summary of extraction mechanisms and representative applica...
Chapter 3
Table 3.1 Advantages and disadvantages of (rapid) equilibrium dialysis (ED) for ...
Table 3.2 Advantages and disadvantages of ultrafiltration for sample preparation...
Table 3.3 Advantages and disadvantages of ultracentrifugation for sample prepara...
Table 3.4 Comparison of the advantages and disadvantages of three methods used f...
Chapter 4
Table 4.1 Summary of sample preparation strategies involved in monito...
Chapter 5
Table 5.1 Salting‐out assisted liquid–liquid extraction procedures for bioanalys...
Chapter 6
Table 6.1 Current applications involving SLE related to bioanalysis.
Table 6.2 Extraction recovery of 10 representative compounds under various extra...
Chapter 7
Table 7.1 Binding, washing, and elution buffers commonly used for immunocapture.
Table 7.2 Affinity of protein A and protein G to IgG subclass from different spe...
Table 7.3 A comparison of immunoglobulin binding proteins.
Chapter 8
Table 8.1 Bioanalytical methods for analysis of drugs and/or metaboli...
Table 8.2 Advantages, disadvantages, and trends of liquid‐phase microextr...
Chapter 9
Table 9.1 Effect of the different technique used to derive plasma for...
Table 9.2 Plasma concentrations of six over‐the‐counter drugs measure...
Table 9.3 Validation statistics for a GSK proprietary compound extrac...
Chapter 10
Table 10.1 A summary of characteristics of the different sample treatments using...
Table 10.2 Number of steps of the different sample treatments using nanomaterial...
Table 10.3 General advantages and disadvantages of the different types of nanoma...
Chapter 11
Table 11.1 Examples of MISPE in pharmaceutical analysis and bioanalys...
Chapter 12
Table 12.1 Examples of SBSE’s applications in bioanalysis.
Chapter 13
Table 13.1 Physicochemical properties of SPE columns.
Table 13.2 Physicochemical properties of commercial MonoSpin columns.
Table 13.3 Representative applications of MonoSpin® extraction in LC‐MS bioanaly...
Chapter 16
Table 16.1 Animal organ weight.
Table 16.2 Commonly used apparatus for tissue homogenization.
Table 16.3 Commonly used agents/enzymes for chemical or enzyme digest...
Table 16.4 Bead size and material selection for tissue interruption. ...
Table 16.5 Vial selection for beads beater tissue homogenization.
Table 16.6 Common parameters for beads beater homogenization (example...
Table 16.7 Homogenization of tissue for the analysis of labile analyt...
Chapter 18
Table 18.1 An example of urine sample preparation procedure using direct ...
Table 18.2 An example of urine sample preparation procedure using LLE....
Table 18.3 An example of urine sample preparation procedure using oasis M...
Table 18.4 An example of cerebrospinal fluid sample preparation procedure...
Table 18.5 An example of CSF sample preparation procedure using direct di...
Table 18.6 An example of synovial fluid sample preparation procedure usin...
Table 18.7 An example of synovial fluid sample preparation procedure usin...
Table 18.8 Sweat sample preparation procedure using direct dilution and f...
Table 18.9 Sweat sample preparation procedure using SPE with Micro SpinCo...
Table 18.10 Examples of tears sample preparation procedure using direct d...
Table 18.11 An example of tears sample preparation procedure using SPE....
Table 18.12 A typical aqueous humor sample preparation procedure using pr...
Table 18.13 An example of aqueous humor sample preparation procedure for ...
Chapter 20
Table 20.1 Proposed study design.
Table 20.2 Assay technical requirements.
Table 20.3 Whole blood sample collection/handling evaluation procedures...
Chapter 21
Table 21.1 Applications of various derivatization strategies.
Chapter 23
Table 23.1 Comparison of different sample preparation strategies for ...
List of Illustrations
Chapter 2
Figure 2.1 A schematic representation of online extraction LC‐MS/MS system with...
Figure 2.2 A schematic representation of online extraction LC‐MS/MS system with...
Chapter 3
Figure 3.1 Schematic representation of the equilibrium dialysis methodology.
Figure 3.2 Rapid equilibrium dialysis (RED) device. Each insert is comprised of...
Figure 3.3 Schematic representation of the ultrafiltration methodology.
Figure 3.4 Schematic representation of the ultracentrifugation methodology.
Chapter 4
Figure 4.1 Frameworks for common phospholipids found in membranes and plasma.
Figure 4.2 (a) (A) LC/MS/MS chromatograms of 250 μg ml
−1
phosphatidylchol...
Figure 4.3 In‐source CID spectra for GPChos at 90 V cone voltage on Quattro Mic...
Figure 4.4 TICs of MRM transitions for five phospholipids remaining in final ex...
Figure 4.5 The UHPLC‐MS/MS chromatograms for matrix (sturgeon) samples spiked w...
Figure 4.6 LC‐MS/MS separation of tamoxifen and its metabolites using steady‐st...
Chapter 5
Figure 5.1 Schematic diagram of the SALLE procedure.
Chapter 6
Figure 6.1 Procedure for supported liquid extraction.
Chapter 7
Figure 7.1 Summary of a typical immunocapture procedure.
Figure 7.2 Examples of different capture reagents.
Figure 7.3 Workflows of typical immunocapture formats. Protein (a), peptide (b)...
Figure 7.4 Evaluation of immunocapture recovery.
Chapter 8
Figure 8.1 Classification of the main microextraction techniques.
Figure 8.2 Main principles of solid‐phase microextraction (SPME) techniques: (a...
Figure 8.3 Main principles of liquid‐phase microextraction (LPME) techniques: (...
Chapter 9
Figure 9.1 Illustration of Drummond Capillary Device for plasma collection and ...
Figure 9.2 Statistical comparisons of air and positive displacement pipettes fo...
Figure 9.3 Illustration of MITRA Device for storage and collection of dried blo...
Figure 9.4 Illustration of MITRA Clamshell Device for storage and shipment of d...
Chapter 10
Figure 10.1 Basic principles of the main extraction techniques used with nanoma...
Figure 10.2 Extraction with MIPs: (a) preparation and (b) principle of MIPs for...
Chapter 11
Figure 11.1 Principle of molecular imprinting.
Figure 11.2 Single ion monitoring chromatograms of BPA, BPA‐
13
C
12
, and BPA‐d
16
...
Figure 11.3 Molecularly imprinted solid‐phase extraction (MISPE) procedure.
Figure 11.4 Experimental configuration of the online two‐step SPE‐LC procedure ...
Figure 11.5 Schematic of preparation of molecularly imprinted microSPE device.
Chapter 12
Figure 12.1 Diagram summarizing the most used methods for trace analysis of com...
Figure 12.2 The increase of β influences the theoretical efficiency of SBSE (PD...
Figure 12.3 Diagram summarizing the SBSE’s operating modes.
Figure 12.4 Illustration of derivatization modes. (a) In situ derivatization, (...
Figure 12.5 The structure of PDMS polymeric phase which has a glass transition ...
Chapter 13
Figure 13.1 Photograph of MonoSpin column (a), and electromicrograph of the dis...
Figure 13.2 General extraction procedure using MonoSpin columns.
Figure 13.3 Representative chromatograms of β‐blockers and calcium blockers obt...
Chapter 14
Figure 14.1 Typical schemes of the preparation of aptamer‐based affinity column...
Figure 14.2 Typical schemes of the preparation of aptamer‐immobilized magnetic ...
Figure 14.3 Scheme of the fabrication process and application of electrospun en...
Chapter 15
Figure 15.1 Typical electromembrane extraction setups for the extraction of aci...
Figure 15.2 Schematic illustration of on‐chip EME.
Figure 15.3 Schematic illustration for drop‐to‐drop EME.
Chapter 16
Figure 16.1 Response of test compound A in different tissues after FAF ultrason...
Figure 16.2 Average concentration of desipramine (a) and fluoxetine (b) in rat ...
Figure 16.3 Microscopic pictures of homogenate solution of mouse heart tissue. ...
Chapter 17
Figure 17.1 Illustration of blood separation for peripheral blood mononuclear c...
Figure 17.2 Illustration of blood separation for peripheral blood mononuclear c...
Chapter 18
Figure 18.1 Generic SPE procedures for biological sample preparation. MCX, mixe...
Figure 18.2 (a) Microduct
®
Sweat Collection System; (b) Microduct Sweat Co...
Figure 18.3 Schirmer’s tear test strips.
Chapter 19
Figure 19.1 Different fractions of the drug in biological samples after adminis...
Figure 19.2 Time course of released (nonencapsulated) doxorubicin (DXR) and lip...
Figure 19.3 Solid‐phase extraction procedure for measurement of encapsulated an...
Chapter 20
Figure 20.1 The work flow of pertinent planning in the pre‐analytical phase bef...
Chapter 21
Figure 21.1 General mechanism of derivatization reactions.
Figure 21.2 Chemical structures of typical derivatization reagents for detectio...
Figure 21.3 Metabolic pathway of prasugrel (Rehmel et al. 2006).
Figure 21.4 Derivatization reaction of the active metabolite of prasugrel (R‐13...
Figure 21.5 Step‐by‐step procedure of derivatization strategy for minodronic ac...
Chapter 22
Figure 22.1 Classes of lipids.
Figure 22.2 ECAPCI/MS/HRMS of 15‐HETE‐PFB. The low‐energy electrons generated f...
Figure 22.3 Typical LC‐ECAPCI/MS/HRMS chromatograms of HETEs as PFB derivatives...
Chapter 23
Figure 23.1 General overview of sample preparation (including sample pretreatme...
Chapter 24
Figure 24.1 Schematic representation of the different components of sample prep...
Figure 24.2 LC‐MS/MS chromatograms for the surrogate peptide of 2.0 ng ml
−1
...
Figure 24.3 Schematic representation of the removal of albumin from plasma by t...
Figure 24.4 Schematic representation of the immunocapture of PTH from human ser...
Figure 24.5 LC‐MS/MS chromatograms for the signature peptide of α1‐antichymotry...
Figure 24.6 Schematic representation of the combination of off‐line protein imm...
Chapter 25
Figure 25.1 The structure of oligonucleotide.
Figure 25.2 2′‐Endo and 3′‐endo conformations of sugar.
Figure 25.3 Schematic of phenol/chloroform LLE.
Figure 25.4 Oligonucleotide isolation by proteinase K digestion.
Figure 25.5 Solid‐phase extraction.
Figure 25.6 Ion‐exchange magnetic bead extraction.
Figure 25.7 Immunoaffinity capture approaches.
Chapter 26
Figure 26.1 Workflow depicting various sample preparation methods for quantitat...
Figure 26.2 Schematic illustration of sample preparation workflows for conjugat...
Figure 26.3 Workflow depicting sample preparation methods for conjugated antibo...
Figure 26.4 Workflow depicting sample preparation methods for total antibody qu...
Figure 26.5 Schematic illustration of sample preparation workflows for DAR anal...
Guide
Cover
Table of Contents
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WILEY SERIES ON PHARMACEUTICAL SCIENCE AND BIOTECHNOLOGY: PRACTICES, APPLICATIONS, AND METHODS
Series Editor:
Mike S. LeeMilestone Development Services
Mike S. Lee (ed.) • Integrated Strategies for Drug Discovery Using Mass Spectrometry
Birendra Pramanik, Mike S. Lee, and Guodong Chen (eds.) • Characterization of Impurities and Degradants Using Mass Spectrometry
Mike S. Lee and Mingshe Zhu (eds.) • Mass Spectrometry in Drug Metabolism and Disposition: Basic Principles and Applications
Mike S. Lee (ed.) • Mass Spectrometry Handbook
Wenkui Li and Mike S. Lee (eds.) • Dried Blood Spots – Applications and Techniques
Wenkui Li, Wenying Jian, and Yunlin Fu (eds.) • Sample Preparation in LC‐MS Bioanalysis
Sample Preparation in LC‐MS Bioanalysis
Edited by
Wenkui Li, Wenying Jian, and Yunlin Fu
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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 bioanalysisDescription: 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–dc23LC record available at https://lccn.loc.gov/2018046969
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List of Contributors
Gilberto Alves, PhDCICS‐UBI – Health Sciences Research CentreUniversity of Beira InteriorCovilhãPortugal
Miguel Ángel Bello‐López, PhDDepartment of Analytical ChemistryUniversidad de SevillaSevillaSpain
Matthew Barfield, PhDResearch and DevelopmentGlaxoSmithKline PharmaceuticalsWareUK
Michael G. Bartlett, PhDDepartment of Pharmaceutical and Biomedical SciencesUniversity of GeorgiaAthens, GAUSA
Babak Basiri, PhDDepartment of Pharmaceutical and Biomedical SciencesUniversity of GeorgiaAthens, GAUSA
Ian A. Blair, PhDDepartment of Systems Pharmacology and Translational TherapeuticsPerelman School of MedicineUniversity of PennsylvaniaPhiladelphia, PAUSA
Chester L. Bowen, MSResearch and DevelopmentGlaxoSmithKline PharmaceuticalsCollegeville, PAUSA
Stacy Brown, PhDDepartment of Pharmaceutical SciencesGatton College of Pharmacy at East Tennessee State UniversityJohnson City, TNUSA
Pilar Campíns‐Falcó, PhDQuímica AnalíticaUniversitat de ValènciaBurjassotSpain
Jennifer Carmical, PharmDDepartment of Pharmaceutical SciencesGatton College of Pharmacy at East Tennessee State UniversityJohnson City, TNUSA
Zhongzhe Cheng, PhDSchool of PharmacyWeifang Medical UniversityWeifang, ShandongChina
Theo de Boer, PhDLC‐MS BioanalysisArdena Bioanalytical Laboratory (ABL)AssenThe Netherlands
Myriam Díaz‐Álvarez, MScDepartment of EnvironmentInstituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA)MadridSpain
Fuyou Du, PhDDepartment of Applied ChemistryGuilin University of TechnologyGuilin, GuangxiChina
Amílcar Falcão, PhDLaboratory of PharmacologyFaculty of PharmacyUniversity of CoimbraCoimbraPortugal
Rut Fernández‐Torres, PhDDepartment of Analytical ChemistryUniversidad de SevillaSevillaSpain
Ana Fortuna, PhDLaboratory of PharmacologyFaculty of PharmacyUniversity of CoimbraCoimbraPortugal
Yunlin Fu, MSPharmacokinetic SciencesNovartis Institutes for BioMedical ResearchEast Hanover, NJUSA
Hong Gao, PhDDrug Metabolism & PharmacokineticsVertex PharmaceuticalsBoston, MAUSA
Rodrigo A. González‐Fuenzalida, PhDQuímica AnalíticaUniversitat de ValènciaBurjassotSpain
Rosa Herráez‐Hernández, PhDQuímica AnalíticaUniversitat de ValènciaBurjassotSpain
Bruce J. Hidy, BScR&D, PPDRichmond, VAUSA
Samuel Hofbauer, BSDepartment of Systems Pharmacology and Translational TherapeuticsUniversity of PennsylvaniaPhiladelphia, PAUSA
Mike (Qingtao) Huang, PhDClinical PharmacologyAkros Pharma Inc.Princeton, NJUSA
Rand G. Jenkins, BSc (retired)PPDMechanicsville, VAUSA
Allena J. Ji, PhD, NRCC, DABCCBiomarkers & Clinical Bioanalyses‐Boston, SanofiFramingham, MAUSA
Wenying Jian, PhDJanssen Research & Development, LLCSpring House, PAUSA
Hongliang Jiang, PhDTongji School of PharmacyHuazhong University of Science and TechnologyWuhan, HubeiChina
Neus Jornet‐Martinez, PhDQuímica AnalíticaUniversitat de ValènciaBurjassotSpain
Maria Kechagia, MScChemistry DepartmentAristotle University of ThessalonikiThessalonikiGreece
Jaeah Kim, PhDDepartment of Pharmaceutical and Biomedical SciencesUniversity of GeorgiaAthens, GAUSA
Maria Kissoudi, MScChemistry DepartmentAristotle University of ThessalonikiThessalonikiGreece
Fumin Li, PhDR&D, PPDMiddleton, WIUSA
Ning Li, PhDDepartment of Pharmaceutical AnalysisSchool of PharmacyShenyang Pharmaceutical UniversityShenyang, LiaoningChina
Wenkui Li, PhDPharmacokinetic SciencesNovartis Institutes for BioMedical ResearchEast Hanover, NJUSA
Ang Liu, PhDBioanalytical SciencesTranslational MedicineBristol‐Myers SquibbPrinceton, NJUSA
Rao N.V.S. Mamidi, PhD, DABTJanssen Research & Development, LLC.Raritan, NJUSA
Yan Mao, PhDDrug Metabolism & PharmacokineticsBoehringer Ingelheim Pharmaceuticals, Inc.Ridgefield, CTUSA
Antonio Martín‐Esteban, PhDDepartment of EnvironmentInstituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA)MadridSpain
Henri Meijering, MScLC‐MS BioanalysisArdena Bioanalytical Laboratory (ABL)AssenThe Netherlands
Clementina Mesaros, PhDDepartment of Systems Pharmacology and Translational TherapeuticsUniversity of PennsylvaniaPhiladelphia, PAUSA
Akira Namera, PhDDepartment of Forensic MedicineGraduate School of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
Ragu Ramanathan, PhDMedicine Design – ADME Sciences, Pfizer, IncGroton, CTUSA
María Ramos‐Payán, PhDDepartment of Analytical ChemistryUniversidad de SevillaSevillaSpain
Márcio Rodrigues, PhDCICS‐UBI – Health Sciences Research CentreUniversity of Beira InteriorCovilhãPortugal
Guihua Ruan, PhDDepartment of Applied ChemistryGuilin University of TechnologyGuilin, GuangxiChina
Takeshi Saito, PhDDepartment of Emergency and Critical Care MedicineTokai University School of MedicineIseharaJapan
Ashkan Salamatipour, BSDepartment of Systems Pharmacology and Translational TherapeuticsUniversity of PennsylvaniaPhiladelphia, PAUSA
Victoria F. Samanidou, PhDChemistry DepartmentAristotle University of ThessalonikiThessalonikiGreece
Nico van de Merbel, PhDPRA Health SciencesAssenThe Netherlands
Cong Wei, PhDDrug Metabolism & Pharmacokinetics, Vertex PharmaceuticalsBoston, MAUSA
Zongyu Wei, MSDepartment of Applied ChemistryGuilin University of TechnologyGuilin, GuangxiChina
Naidong Weng, PhDJanssen Research & Development, LLC.Spring House, PAUSA
John Williams, PhDDrug Metabolism & Pharmacokinetics Vertex PharmaceuticalsBoston, MAUSA
Xin Xiong, MSDepartment of PharmacyPeking University Third HospitalBeijingChina
Long Yuan, PhDBioanalytical SciencesBristol‐Myers SquibbPrinceton, NJUSA
Qiulian Zeng, MSDepartment of Applied ChemistryGuilin University of TechnologyGuilin, GuangxiChina
Jun Zhang, PhDDynamega LLCLake Forest, ILUSA
Dafang Zhong, PhDShanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina
Yunting Zhu, PhDShanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina
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, PhDWenying Jian, PhDYunlin 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‐C
4
D
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‐Δ
9
‐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
TXB
2
thromboxane B
2
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
