Handbook of LC–MS Bioanalysis: Best Practices, Experimental Protocols, and Regulations

Consolidates the information LC-MS bioanalytical scientists need to analyze small molecules and macromolecules The field of bioanalysis has advanced rapidly, propelled by new approaches for developing bioanalytical methods, new liquid chromatographic (LC) techniques, and new mass spectrometric (MS) instruments. Moreover, there are a host of guidelines and regulations designed to ensure the quality of bioanalytical results. Presenting the best practices, experimental protocols, and the latest understanding of regulations, this book offers a comprehensive review of LC-MS bioanalysis of small molecules and macromolecules. It not only addresses the needs of bioanalytical scientists working on routine projects, but also explores advanced and emerging technologies such as high-resolution mass spectrometry and dried blood spot microsampling. Handbook of LC-MS Bioanalysis features contributions from an international team of leading bioanalytical scientists. Their contributions reflect a review of the latest findings, practices, and regulations as well as their own firsthand analytical laboratory experience. The book thoroughly examines: Fundamentals of LC-MS bioanalysis in drug discovery, drug development, and therapeutic drug monitoring The current understanding of regulations governing LC-MS bioanalysis Best practices and detailed technical instructions for LC-MS bioanalysis method development, validation, and stability assessment of analyte(s) of interest Experimental guidelines and protocols for quantitative LC-MS bioanalysis of challenging molecules, including pro-drugs, acyl glucuronides, N-oxides, reactive compounds, and photosensitive and autooxidative compounds With its focus on current bioanalytical practice, Handbook of LC-MS Bioanalysis enables bioanalytical scientists to develop and validate robust LC-MS assay methods, all in compliance with current regulations and standards.

Editors’ Preface Wenkui Li, Jie Zhang and Francis LS Tse Part I: Overview of LC–MS Bioanalysis 1. Roles of LC–MS Bioanalysis in Drug Discovery, Development and Therapeutic Drug Monitoring Steve Unger, Wenkui Li, Jimmy Flarakos and Francis L.S. Tse 2. Overview: Fundamentals of a Bioanalytical Laboratory Naidong Weng, Shefali Patel, Qiangtao (Mike) Huang, Wenying Jian, and Richard Edom 3. International Regulations and Quality Standards of Bioanalysis Surendra Bansal Part II: Current Understanding of LC–MS Bioanalysis–Related Regulations 4. Current Regulations for Bioanalytical Method Validations Mark E. Arnold, Rafael E. Barrientos–Astigarraga, Fabio Garofolo, Shinobu Kudoh, Shrinivas S. Savale, Shinobu Kudoh, Daniel Tang, Philip Timmerman and Peter van Amsterdam 5. Current Understanding of Bioanalytical Assay Reproducibility – Incurred Sample Reanalysis (ISR), Incurred Sample Stability (ISS) and Incurred Sample Accuracy (ISA) Manish Yadav, Pranav S. Shrivastav, Theo de Boer, Jaap Wieling, and Puran Singhal 6. LC–MS Bioanalytical Method Transfer Zhongping (John) Lin, Wenkui Li and Naidong Weng, 7. Metabolites in Safety Testing (MIST) Ragu Ramanathan and Dil M. Ramanathan 8. A Comparison of FDA, EMA, ANVISA, and Others on Bioanalysis in Support of Bioequivalence / Bioavailability Studies Bradley Nash 9. Comparison of the Guidance of FDA, OECD, EPA and Others on Good Laboratory Practice J. Kirk Smith 10. Current Understanding of Bioanalysis Data Management and Trend of Regulations on Data Management Zhongping (John) Lin, Jianing Zeng, Joe Rajarao, Michael Moyer and Michael Hayes 11. Regulatory Inspections Trends and Findings of Bioanalytical Laboratory Frank Chow, Martin Yau, and Leon Lachman, Part III: Best Practice in LC–MS Bioanalysis 12. Assessment of Whole Blood Stability and Blood/Plasma Distribution of Drugs Iain Love, Graeme T. Smith and Howard M. Hill 13. Best Practice in Biological Sample Collection, Processing and Storage for LC–MS Bioanalysis of Drugs Maria Pawula, Glen Hawthorne, Graeme T. Smith and Howard M. Hill 14. Best Practice in Biological Sample Preparation for LC–MS Bioanalysis Guowen Liu and Anne–Francoise Aubry 15. Best Practice in Liquid Chromatography for LC–MS Bioanalysis Steve Unger and Naidong Weng 16. Best Practice in Mass Spectrometry for LC–MS Richard van Breemen and Elizabeth M. Martinez 17. Use of Internal Standard in LC–MS Bioanalysis Aimin Tan and Kayode Awaiye 18. System Suitability in LC–MS Bioanalysis Chad Briscoe 19. Derivatization in LC–MS Bioanalysis Tomofumi Santa 20. Evaluation and Elimination of Matrix Effect in LC–MS Bioanalysis Christopher A. James and Bernd Bruenner 21. Evaluation and Elimination of Carryover and/or Contamination in LC–MS Bioanalysis Howard M. Hill and Graeme T. Smith 22. Automation in LC–MS Bioanalysis Joseph Tweed 23. LC–MS/MS Bioanalysis of Drugs in Tissue Samples Hong Gao, Stacy Ho and John Williams 24. LC–MS Bioanalysis of Drugs in Urine Allena J. Ji 25. LC–MS Bioanalysis of Unbound Drugs in Plasma and Serum Theo de Boer and Jaap Wieling 26. LC–MS Bioanalysis of Drugs in Biles Hong Gao and John Williams 27. LC–MS Bioanalysis of Intracellular Drugs Fagen (Frank) Zhang and Michael Bartels 28. LC–MS LC–MS Bioanalysis of Endogenous Compounds as Biomarkers Wenying Jian, Richard Edom and Naidong Weng 29. LC–MS Bioanalysis of Drugs in Hemolyzed and Lipemic Samples Min Meng, Spencer Carter and Patrick Bennett 30. Best Practice in LC–MS Method Development and Validation for Dried Blood Spots (DBS) Jie Zhang, Tapan K. Majumdar, Jimmy Flarakos and Francis Tse 31. LC–MS Method Development Strategies for Enhancing Mass Spectrometric Detection Yuan–Qing Xia and Jeffrey D. Miller 32. LC–MS Bioanalysis–related Statistics David Hoffman 33. Simultaneous LC–MS Quantitation and Metabolite Identification in Drug Metabolism and Pharmacokinetics Patrick Rudewicz Part IV: Representative Guidelines and/or Experimental Protocols of LC–MS Bioanalysis 34. LC–MS/MS Bioanalysis of Ester Prodrugs and Other Esterase Labile Molecules Wenkui Li, Yunlin Fu, Jimmy Flarakos and Duxi Zhang 35. LC–MS Bioanalysis of Acyl Glucurorides Jin Zhou and Jeffery X. Duggan and Feng (Frank) Li 36. Regulated bioassay of N–oxide metabolites using LC–MS: Dealing with potential instability issues Tapan K. Majumdar 37. Hydrolysis (Acidic or Enzymatic) of Phase II Conjugates for LC–MS Bioanalysis of Total Parent Drugs Laixin Wang, Weiwei Yuan, Scott Reuschel and Min Meng 38. LC–MS Bioanalysis of Reactive Compounds Hermes Licea–Perez, Christopher Evans and Yi (Eric) Yang 39. LC–MS Bioanalysis of Photosensitive and Autooxidative Compounds Corey Ohnmacht 40. LC–MS Bioanalysis of Interconvertible Compounds Nico van de Merbel 41. LC–MS Bioanalysis of Chiral Compounds Naidong Weng 42. LC–MS Bioanalysis of Peptides and Polypeptides Christopher A. James and Hongyan Li 43. LC–MS Bioanalysis of Nucleosides Laixin Wang and Min Meng 44. LC–MS Bioanalysis of Nucleotides Sabine Cohen, Marie–Claude Gagnieu, Isabelle Lefebvre and Jérôme Guitton 45. LC–MS Bioanalysis of Steroids Jie Zhang and Frank Stanczyk 46. LC–MS/MS Bioanalysis of Bioanalysis of Liposomal Drugs and Lipids Troy Voelker and Roger Demers 47. LC–MS Bioanalysis of Proteins Ziping Yang, Wenkui Li, Harold T. Smith and Francis L.S. Tse, Novartis 48. Liquid Chromatography–Mass Spectrometric Bioanalysis of Oligonucleotides Michael G. Bartlett, Buyun Chen and A. Cary McGinnis 49. LC–MS Bioanalysis of Platinum Drugs Troy Voelker and Min Meng 50. Micro–flow LC–MS for Quantitative Analysis of Drugs in Support of Microsampling Heather Skor and Sadayappan V. Rahavendran 51. Quantification of Endogenous Analytes in Biofluids by a Combination of Liquid Chromatography–Mass Spectrometry and Construction of Calibration Curves Using Stable–Isotopes as Surrogate Analytes with True Biological Control Matrices Wenlin (Wendy) Li, Lucinda Cohen and Erick Kindt Appendix: 1. Common Biological Matrices and Respective Physiological Properties 2. Anticoagulants and Other Addictives Commonly Used in Biological Sample Collection 3. Buffers, Reagents and Mobile Phase Additives Commonly Used in LC–MS Bioanalysis 4. Common Terms and Instrument Parameters of LC–MS Bioanalysis 5. Abbreviation

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.