Handbook of LC-MS Bioanalysis

Preface xi

Contributors xiii

Abbreviations xvii

Part I Overview of LC-MS Bioanalysis

1 Roles of LC-MS Bioanalysis in Drug Discovery, Development, and Therapeutic Drug Monitoring 3
Steve Unger, Wenkui Li, Jimmy Flarakos, and Francis L.S. Tse

2 Overview: Fundamentals of a Bioanalytical Laboratory 15
Shefali Patel, Qiangtao (Mike) Huang, Wenying Jian, Richard Edom, and Naidong Weng

3 International Regulations and Quality Standards of Bioanalysis 29
Surendra K. Bansal

Part II Current Understanding of LC-MS Bioanalysis-related Regulations

4 Current Regulations for Bioanalytical Method Validations 39
Mark E. Arnold, Rafael E. Barrientos-Astigarraga, Fabio Garofolo, Shinobu Kudoh, Shrinivas S. Savale, Daniel Tang, Philip Timmerman, and Peter van Amsterdam

5 Current Understanding of Bioanalytical Assay Reproducibility: Incurred Sample Reanalysis, Incurred Sample Stability, and Incurred Sample Accuracy 47
Manish S. Yadav, Pranav S. Shrivastav, Theo de Boer, Jaap Wieling, and Puran Singhal

6 LC-MS Bioanalytical Method Transfer 65
Zhongping (John) Lin, Wenkui Li, and Naidong Weng

7 Metabolites in Safety Testing 71
Ragu Ramanathan and Dil M. Ramanathan

8 A Comparison of FDA, EMA, ANVISA, and Others on Bioanalysis in Support of Bioequivalence/ Bioavailability Studies 83
Bradley Nash

9 A Comparison of the Guidance of FDA, OECD, EPA, and Others on Good Laboratory Practice 89
J. Kirk Smith

10 Current Understanding of Bioanalysis Data Management and Trend of Regulations on Data Management 97
Zhongping (John) Lin, Michael Moyer, Jianing Zeng, Joe Rajarao, and Michael Hayes

11 Regulatory Inspection Trends and Findings of Bioanalytical Laboratories 109
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 129
Iain Love, Graeme T. Smith, and Howard M. Hill

13 Best Practice in Biological Sample Collection, Processing, and Storage for LC-MS in Bioanalysis of Drugs 139
Maria Pawula, Glen Hawthorne, Graeme T. Smith, and Howard M. Hill

14 Best Practices in Biological Sample Preparation for LC-MS Bioanalysis 165
Guowen Liu and Anne-Françoise Aubry

15 Best Practice in Liquid Chromatography for LC-MS Bioanalysis 185
Steve Unger and Naidong Weng

16 Best Practice in Mass Spectrometry for LC-MS 205
Richard B. van Breemen and Elizabeth M. Martinez

17 Use of Internal Standards in LC-MS Bioanalysis 217
Aimin Tan and Kayode Awaiye

18 System Suitability in LC-MS Bioanalysis 229
Chad Briscoe

19 Derivatization in LC-MS Bioanalysis 239
Tomofumi Santa

20 Evaluation and Elimination of Matrix Effects in LC-MS Bioanalysis 249
Bernd A. Bruenner and Christopher A. James

21 Evaluation and Elimination of Carryover and/or Contamination in LC-MS Bioanalysis 259
Howard M. Hill and Graeme T. Smith

22 Automation in LC-MS Bioanalysis 275
Joseph A. Tweed

23 LC-MS Bioanalysis of Drugs in Tissue Samples 297
Hong Gao, Stacy Ho, and John Williams

24 LC-MS Bioanalysis of Drugs in Urine 307
Allena J. Ji

25 LC-MS Bioanalysis of Unbound Drugs in Plasma and Serum 317
Theo de Boer and Jaap Wieling

26 LC-MS Bioanalysis of Drugs in Bile 327
Hong Gao and John Williams

27 LC-MS Bioanalysis of Intracellular Drugs 337
Fagen Zhang and Michael J. Bartels

28 LC-MS Bioanalysis of Endogenous Compounds as Biomarkers 353
Wenying Jian, Richard Edom, and Naidong Weng

29 LC-MS Bioanalysis of Drugs in Hemolyzed and Lipemic Samples 369
Min Meng, Spencer Carter, and Patrick Bennett

30 Best Practices in LC-MS Method Development and Validation for Dried Blood Spots 379
Jie Zhang, Tapan K. Majumdar, Jimmy Flarakos, and Francis L.S. Tse

31 LC-MS Method Development Strategies for Enhancing Mass Spectrometric Detection 391
Yuan-Qing Xia and Jeffrey D. Miller

32 LC-MS Bioanalysis-Related Statistics 403
David Hoffman

33 Simultaneous LC-MS Quantitation and Metabolite Identification in Drug Metabolism and Pharmacokinetics 417
Patrick J. Rudewicz

Part IV Representative Guidelines and/or Experimental Protocols of LC-MS Bioanalysis

34 LC-MS Bioanalysis of Ester Prodrugs and Other Esterase Labile Molecules 431
Wenkui Li, Yunlin Fu, Jimmy Flarakos, and Duxi Zhang

35 LC-MS Bioanalysis of Acyl Glucuronides 447
Jin Zhou, Feng (Frank) Li, and Jeffery X. Duggan

36 Regulated Bioassay of N-Oxide Metabolites Using LC-MS: Dealing with Potential Instability Issues 461
Tapan K. Majumdar

37 Hydrolysis of Phase II Conjugates for LC-MS Bioanalysis of Total Parent Drugs 471
Laixin Wang, Weiwei Yuan, Scott Reuschel, and Min Meng

38 LC-MS Bioanalysis of Reactive Compounds 479
Hermes Licea-Perez, Christopher A. Evans, and Yi (Eric) Yang

39 LC-MS Bioanalysis of Photosensitive and Oxidatively Labile Compounds 491
Corey M. Ohnmacht

40 LC-MS Bioanalysis of Interconvertible Compounds 505
Nico van de Merbel

41 LC-MS Bioanalysis of Chiral Compounds 519
Naidong Weng

42 LC-MS Bioanalysis of Peptides and Polypeptides 535
Hongyan Li and Christopher A. James

43 LC-MS Bioanalysis of Nucleosides 551
Laixin Wang and Min Meng

44 LC-MS Bioanalysis of Nucleotides 559
Sabine Cohen, Marie-Claude Gagnieu, Isabelle Lefebvre, and Jérôme Guitton

45 LC-MS Bioanalysis of Steroids 573
Jie Zhang and Frank Z. Stanczyk

46 LC-MS Bioanalysis of Liposomal Drugs and Lipids 591
Troy Voelker and Roger Demers

47 LC-MS Bioanalysis of Proteins 601
Ziping Yang, Wenkui Li, Harold T. Smith, and Francis L.S. Tse

48 LC-MS Bioanalysis of Oligonucleotides 607
Michael G. Bartlett, Buyun Chen, and A. Cary McGinnis

49 LC-MS Bioanalysis of Platinum Drugs 629
Troy Voelker and Min Meng

50 Microflow LC-MS for Quantitative Analysis of Drugs in Support of Microsampling 639
Heather Skor and Sadayappan V. Rahavendran

51 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 649
Wenlin Li, Lucinda Cohen, and Erick Kindt

Appendix 1 Body and Organ Weights and Physiological Parameters in Laboratory Animals and Humans 659

Appendix 2 Anticoagulants Commonly Used in Blood Sample Collection 661

Appendix 3 Solvents and Reagents Commonly Used in LC-MS Bioanalysis 663

Appendix 4 Glossary of Terms Used in LC-MS Bioanalysis 665

Index 673