Handbook of LC-MS Bioanalysis

WENKUI LI, PhD, is Senior Fellow in the Department of Drug Metabolism & Pharmacokinetics at Novartis Institutes for BioMedical Research, where he focuses on regulated LC-MS/MS bioanalysis for the toxicokinetic and pharmacokinetic assessment of drug candidates. Dr. Li is a member of the editorial board of Biomedical Chromatography.JIE ZHANG, PhD, is Senior Fellow in the Department of Drug Metabolism & Pharmacokinetics at Novartis Institutes for BioMedical Research, where he focuses on regulated LC-MS bioanalysis for the toxicokinetic and pharmacokinetic assessment of drug candidates. In addition, Dr. Zhang evaluates and implements novel technologies and processes in regulated LC-MS bioanalysis.FRANCIS L. S. TSE, PhD, is Vice President of Drug Metabolism & Bioanalytics at Novartis Institutes for BioMedical Research, overseeing the unit's strategy and operations in North America and Asia. Dr. Tse is a Fellow of the American Association of Pharmaceutical Scientists, APhA Academy of Pharmaceutical Research and Science, and American College of Clinical Pharmacology.

• Preface xiContributors xiiiAbbreviations xviiPart I Overview of LC-MS Bioanalysis1 Roles of LC-MS Bioanalysis in Drug Discovery, Development, and Therapeutic Drug Monitoring 3Steve Unger, Wenkui Li, Jimmy Flarakos, and Francis L.S. Tse2 Overview: Fundamentals of a Bioanalytical Laboratory 15Shefali Patel, Qiangtao (Mike) Huang, Wenying Jian, Richard Edom, and Naidong Weng3 International Regulations and Quality Standards of Bioanalysis 29Surendra K. BansalPart II Current Understanding of LC-MS Bioanalysis-related Regulations4 Current Regulations for Bioanalytical Method Validations 39Mark E. Arnold, Rafael E. Barrientos-Astigarraga, Fabio Garofolo, Shinobu Kudoh, Shrinivas S. Savale, Daniel Tang, Philip Timmerman, and Peter van Amsterdam5 Current Understanding of Bioanalytical Assay Reproducibility: Incurred Sample Reanalysis, Incurred Sample Stability, and Incurred Sample Accuracy 47Manish S. Yadav, Pranav S. Shrivastav, Theo de Boer, Jaap Wieling, and Puran Singhal6 LC-MS Bioanalytical Method Transfer 65Zhongping (John) Lin, Wenkui Li, and Naidong Weng7 Metabolites in Safety Testing 71Ragu Ramanathan and Dil M. Ramanathan8 A Comparison of FDA, EMA, ANVISA, and Others on Bioanalysis in Support of Bioequivalence/ Bioavailability Studies 83Bradley Nash9 A Comparison of the Guidance of FDA, OECD, EPA, and Others on Good Laboratory Practice 89J. Kirk Smith10 Current Understanding of Bioanalysis Data Management and Trend of Regulations on Data Management 97Zhongping (John) Lin, Michael Moyer, Jianing Zeng, Joe Rajarao, and Michael Hayes11 Regulatory Inspection Trends and Findings of Bioanalytical Laboratories 109Frank Chow, Martin Yau, and Leon LachmanPart III Best Practice in LC-MS Bioanalysis12 Assessment of Whole Blood Stability and Blood/Plasma Distribution of Drugs 129Iain Love, Graeme T. Smith, and Howard M. Hill13 Best Practice in Biological Sample Collection, Processing, and Storage for LC-MS in Bioanalysis of Drugs 139Maria Pawula, Glen Hawthorne, Graeme T. Smith, and Howard M. Hill14 Best Practices in Biological Sample Preparation for LC-MS Bioanalysis 165Guowen Liu and Anne-Françoise Aubry15 Best Practice in Liquid Chromatography for LC-MS Bioanalysis 185Steve Unger and Naidong Weng16 Best Practice in Mass Spectrometry for LC-MS 205Richard B. van Breemen and Elizabeth M. Martinez17 Use of Internal Standards in LC-MS Bioanalysis 217Aimin Tan and Kayode Awaiye18 System Suitability in LC-MS Bioanalysis 229Chad Briscoe19 Derivatization in LC-MS Bioanalysis 239Tomofumi Santa20 Evaluation and Elimination of Matrix Effects in LC-MS Bioanalysis 249Bernd A. Bruenner and Christopher A. James21 Evaluation and Elimination of Carryover and/or Contamination in LC-MS Bioanalysis 259Howard M. Hill and Graeme T. Smith22 Automation in LC-MS Bioanalysis 275Joseph A. Tweed23 LC-MS Bioanalysis of Drugs in Tissue Samples 297Hong Gao, Stacy Ho, and John Williams24 LC-MS Bioanalysis of Drugs in Urine 307Allena J. Ji25 LC-MS Bioanalysis of Unbound Drugs in Plasma and Serum 317Theo de Boer and Jaap Wieling26 LC-MS Bioanalysis of Drugs in Bile 327Hong Gao and John Williams27 LC-MS Bioanalysis of Intracellular Drugs 337Fagen Zhang and Michael J. Bartels28 LC-MS Bioanalysis of Endogenous Compounds as Biomarkers 353Wenying Jian, Richard Edom, and Naidong Weng29 LC-MS Bioanalysis of Drugs in Hemolyzed and Lipemic Samples 369Min Meng, Spencer Carter, and Patrick Bennett30 Best Practices in LC-MS Method Development and Validation for Dried Blood Spots 379Jie Zhang, Tapan K. Majumdar, Jimmy Flarakos, and Francis L.S. Tse31 LC-MS Method Development Strategies for Enhancing Mass Spectrometric Detection 391Yuan-Qing Xia and Jeffrey D. Miller32 LC-MS Bioanalysis-Related Statistics 403David Hoffman33 Simultaneous LC-MS Quantitation and Metabolite Identification in Drug Metabolism and Pharmacokinetics 417Patrick J. RudewiczPart IV Representative Guidelines and/or Experimental Protocols of LC-MS Bioanalysis34 LC-MS Bioanalysis of Ester Prodrugs and Other Esterase Labile Molecules 431Wenkui Li, Yunlin Fu, Jimmy Flarakos, and Duxi Zhang35 LC-MS Bioanalysis of Acyl Glucuronides 447Jin Zhou, Feng (Frank) Li, and Jeffery X. Duggan36 Regulated Bioassay of N-Oxide Metabolites Using LC-MS: Dealing with Potential Instability Issues 461Tapan K. Majumdar37 Hydrolysis of Phase II Conjugates for LC-MS Bioanalysis of Total Parent Drugs 471Laixin Wang, Weiwei Yuan, Scott Reuschel, and Min Meng38 LC-MS Bioanalysis of Reactive Compounds 479Hermes Licea-Perez, Christopher A. Evans, and Yi (Eric) Yang39 LC-MS Bioanalysis of Photosensitive and Oxidatively Labile Compounds 491Corey M. Ohnmacht40 LC-MS Bioanalysis of Interconvertible Compounds 505Nico van de Merbel41 LC-MS Bioanalysis of Chiral Compounds 519Naidong Weng42 LC-MS Bioanalysis of Peptides and Polypeptides 535Hongyan Li and Christopher A. James43 LC-MS Bioanalysis of Nucleosides 551Laixin Wang and Min Meng44 LC-MS Bioanalysis of Nucleotides 559Sabine Cohen, Marie-Claude Gagnieu, Isabelle Lefebvre, and Jérôme Guitton45 LC-MS Bioanalysis of Steroids 573Jie Zhang and Frank Z. Stanczyk46 LC-MS Bioanalysis of Liposomal Drugs and Lipids 591Troy Voelker and Roger Demers47 LC-MS Bioanalysis of Proteins 601Ziping Yang, Wenkui Li, Harold T. Smith, and Francis L.S. Tse48 LC-MS Bioanalysis of Oligonucleotides 607Michael G. Bartlett, Buyun Chen, and A. Cary McGinnis49 LC-MS Bioanalysis of Platinum Drugs 629Troy Voelker and Min Meng50 Microflow LC-MS for Quantitative Analysis of Drugs in Support of Microsampling 639Heather Skor and Sadayappan V. Rahavendran51 Quantification of Endogenous Analytes in Biofluids by a Combination of LC-MS and Construction of Calibration Curves Using Stable-Isotopes as Surrogate Analytes with True Biological Control Matrices 649Wenlin Li, Lucinda Cohen, and Erick KindtAppendix 1 Body and Organ Weights and Physiological Parameters in Laboratory Animals and Humans 659Appendix 2 Anticoagulants Commonly Used in Blood Sample Collection 661Appendix 3 Solvents and Reagents Commonly Used in LC-MS Bioanalysis 663Appendix 4 Glossary of Terms Used in LC-MS Bioanalysis 665Index 673

“In that, it serves as a source of information and of literature references for further in-depth reading. It is very useful to have but, like always, it does not give all answers to every question one may have.”  (ChemMedChem, 1 June 2014)