Mass Spectrometry for the Clinical Laboratory

Mass Spectrometry for the Clinical Laboratory is an accessible guide to mass spectrometry and the development, validation, and implementation of the most common assays seen in clinical labs. It provides readers with practical examples for assay development, and experimental design for validation to meet CLIA requirements, appropriate interference testing, measuring, validation of ion suppression/matrix effects, and quality control. These tools offer guidance on what type of instrumentation is optimal for each assay, what options are available, and the pros and cons of each. Readers will find a full set of tools that are either directly related to the assay they want to adopt or for an analogous assay they could use as an example.

Written by expert users of the most common assays found in a clinical laboratory (clinical chemists, toxicologists, and clinical pathologists practicing mass spectrometry), the book lays out how experts in the field have chosen their mass spectrometers, purchased, installed, validated, and brought them on line for routine testing.

The early chapters of the book covers what the practitioners have learned from years of experience, the challenges they have faced, and their recommendations on how to build and validate assays to avoid problems. These chapters also include recommendations for maintaining continuity of quality in testing. The later parts of the book focuses on specific types of assays (therapeutic drugs, Vitamin D, hormones, etc.). Each chapter in this section has been written by an expert practitioner of an assay that is currently running in his or her clinical lab.

• Provides readers with the keys to choosing, installing, and validating a mass spectrometry platform
• Offers tools to evaluate, validate, and troubleshoot the most common assays seen in clinical pathology labs
• Explains validation, ion suppression, interference testing, and quality control design to the detail that is required for implementation in the lab

Residents and fellows in clinical pathology and clinical chemistry, practicing clinical pathologists and clinical chemists

• List of Contributors
• Preface
• Chapter 1: Mass spectrometry in the clinical laboratory: determining the need and avoiding pitfalls
  • Abstract
  • 1. Clinical mass spectrometry
• Chapter 2: Application specific implementation of mass spectrometry platform in clinical laboratories
  • Abstract
  • 1. Mass spectrometry versus automated immunoassay platforms
  • 2. Early decisions in the implementation of mass spectrometry in the laboratory
  • 3. Importance of internal standards in mass spectrometry
  • 4. Matrix effects, extraction efficiency, and ion suppression/enhancement
  • 5. Analyte extraction
  • 6. Choice of separation technique: GC versus LC
  • 7. Choice of stationary phase
  • 8. Choice of ionization techniques
  • 9. Choice of mass analyzer
  • 10. Summary
• Chapter 3: Sample preparation techniques for mass spectrometry in the clinical laboratory
  • Abstract
  • 1. Why is sample preparation needed for LC-MS/MS?
  • 2. Selecting a sample preparation protocol
  • 3. Description of commonly used clinical sample preparation protocols
  • 4. Evaluation of sample preparation protocols
  • 5. Comparison of sample preparation protocols
  • 6. Optimization of sample preparation protocols
  • 7. Summary
• Chapter 4: Validation, quality control, and compliance practice for mass spectrometry assays in the clinical laboratory
  • Abstract
  • 1. Introduction
  • 2. Elements of assay validation according to CLIA, CAP, and FDA guidelines
  • 3. Elements of quality control
  • 4. Regulatory compliance
  • 5. Additional resources from the literature
  • 6. Summary
• Chapter 5: Best practices for routine operation of clinical mass spectrometry assays
  • Abstract
  • 1. New assay implementation
  • 2. System suitability standards
  • 3. Verification of new materials
  • 4. Sample analysis
  • 5. Data review
  • 6. Instrument maintenance
  • 7. Quality assurance for specimen analysis
  • 8. Conclusions
• Chapter 6: Toxicology: liquid chromatography mass spectrometry
  • Abstract
  • 1. Toxicology testing in the clinical laboratory
  • 2. Chromatographic methods for toxicology testing in the clinical laboratory
  • 3. Toxicology LC-MS applications
  • 4. Conclusions
• Chapter 7: Toxicology: GCMS
  • Abstract
  • 1. Use and strengths of GC-MS in clinical toxicology
  • 2. Limitations of GC-MS in clinical toxicology
  • 3. Instrument selection
  • 4. Defining an assay method
  • 5. Analysis
  • 6. Assay validation
  • 7. Instrument maintenance and troubleshooting
  • 8. Personnel/training
• Chapter 8: Therapeutic drug monitoring using mass spectrometry
  • Abstract
  • 1. Background/introduction
  • 2. MS considerations for TDM
  • 3. Assay design/test life cycle considerations
  • 4. Sample preparation considerations
  • 5. Validation considerations
  • 6. Quality control/quality assurance considerations
  • 7. Conclusions
• Chapter 9: Vitamin D metabolite quantitation by LC-MS/MS
  • Abstract
  • 1. Physiological role of vitamin D
  • 2. Evolution of assays for vitamin D metabolites
  • 3. Clinical utility and quantitation of vitamin D and its metabolites by LC-MS/MS
  • 4. Conclusions
• Chapter 10: Steroid hormones
  • Abstract
  • 1. Steroid hormone applications for clinical use
  • 2. Calibration and quality control requirements
  • 3. Sample preparation
  • 4. Instrumentation
  • 5. Validation
  • 6. Postimplementation Monitoring
  • 7. Preanalytical considerations
  • 8. Postanalytical considerations
  • Disclaimer
• Chapter 11: Mass spectrometry in the clinical microbiology laboratory
  • Abstract
  • 1. Introduction
  • 2. How MALDI-TOF MS works
  • 3. Commercial systems
  • 4. Bacteriology
  • 5. Mycobacteriology
  • 6. Mycology
  • 7. Other Possible MALDI-TOF MS Applications
  • 8. Other MS technologies
  • 9. Summary and Conclusions
• Chapter 12: High resolution accurate mass (HRAM) mass spectrometry
  • Abstract
  • 1. Introduction
  • 2. HRMS fundamentals
  • 3. Clinical and forensic toxicology
  • 4. Microbiology
  • 5. Molecular diagnostics
  • 6. Future HRMS clinical applications and developments
  • 7. Conclusions
• Chapter 13: Evolving platforms for clinical mass spectrometry
  • Abstract
  • 1. Introduction
  • 2. Triple quadrupole
  • 3. Quadrupole-time of flight (TOF) and TOF
  • 4. Ion trap and orbitrap
  • 5. MALDI-TOF
  • 6. Hybrid instruments
  • 7. PCR-MS
  • 8. Front end—sample preparation and collection/ambient ionization/real time analysis
  • 9. Ambient and direct ionization approaches
  • 10. Imaging MS
  • 11. DESI imaging
  • 12. Ion mobility mass spectrometry
  • 13. Proteomics
  • 14. Future implications
• Index