LC-MS

1st Asia Pacific Bioanalytical Conference (1st APBC)

"Bringing together scientists from across Asia Pacific and the rest of the world to discuss, review, share perspectives,
provide potential solutions and agree upon consistent approaches on the recent issues in GLP regulated bioanalysis"

January 12-13, 2011, Shanghai, China
Pre-Conference Short Course: January 11, 2011
Post-Conference Site Visits and Tour: January 14, 2011

Conference Report  |   Introduction  |   Speaker List  |   Final Program Agenda   |   Short Course   |   Sponsors  

 

Pre-Conference Short Course

8am-5pm, January 11, 2011
Tutorial in Regulated Bioanalysis: Bioanalytical Method Validation (BMV) and Sample Analysis for Chromatographic and Ligand Binding Assays (LBA)

Bioanalytical Method Validation: "History & Definitions"

  • Definition of Bioanalytical Method Validation
  • Regulatory Guidance on Bioanalytical Method Validation from Crystal City I to Crystal City III
  • FDA Guidance for the Industry, Bioanalytical Method Validation (May 2001)
  • FDA Good Laboratory Practice for Nonclinical Laboratory Studies: Title 21, Code of Federal Regulations, Part 58
  • OECD Principles on Good Laboratory Practice (as revised in 1997)
  • Drugs Directorate Guidelines, "Conduct and Analysis of Bioavailability and Bioequivalence Studies"
  • Statistics in Bioanalysis
    • Statistical Mean
    • Standard Deviation and Relative Standard Deviation
    • Deviation from Theoretical and Percent Difference
    • Correlation Coefficient
    • Rejection of Outliers with T-test
  • GLP Definitions
  • Key Terms & Concepts in Bioanalysis
  • GLP Documentation
    • Analytical Method
    • Data Review

Bioanalytical Method Validation: "Criteria & Concepts"

  • The Validation Process and the Validation Goals
  • Uncertainty in Quantitative Analysis
  • Validation Parameters and Method Validation
    • Accuracy and Precision
    • Analysis of Variance (ANOVA)
    • Assessing Accuracy and Precision
    • Stability Tests
    • Recovery
  • Approaches to Quantification
    • Calibration Curve
      • Limit of Quantification (LLOQ & ULOQ) and other Key Terms
      • Quantitative Relationships in MS Instruments
      • Nature of Regression Errors
    • Standard Addition
  • Defining Acceptance Criteria
  • Essential Documentation
  • System Suitability and its Importance
  • The Steps in a Typical MS Quantitative Analysis
  • Routine Sample Analysis

LC-MS/MS & Bioanalysis

  • Why LC-MS/MS?
    • Advantages & Disadvantages of using LC-MS/MS in Bioanalysis
  • Professor Fred McLafferty's Four S's of LC-MS Analysis
  • Internal Standard
    • Importance of Choosing the best Internal Standard
    • Analogue vs. Stable Labeled Internal Standards
    • D, C13, N15 internal standards
  • Sample Preparation Pros and Con
    • Protein Precipitation (PPT)
    • Liquid-Liquid Extraction (LLE)
    • Solid Phase Extraction (SPE)
  • Matrix Effect and Ion Suppression/Enhancement Definitions
  • Carryover Definition

Ligand Binding Assays (LBA) & Bioanalysis

  • A Special Case: Quantitative Analysis of Therapeutic Bioactive Proteins
  • Background and basics
    • Yalow & Berson
    • Antibodies and Antigens
  • Types of Immunoassays
    • Competitive Immunoassay
    • Non-competitive Immunoassay
    • Heterogeneous vs Homogenous Immunoassays
    • RIA,EIA,FPIA, KIMS, Lateral Flow
    • ELISA
  • LBA: Strength and Limitations
  • Cross-Reactivity Issues
  • Testing Formats and Models
  • LC-MS/MS vs. LBA
    • Types of LBA Protocols
    • Reagents vs. Equipment
    • Detector System
    • Reference Standard
    • Calibration Curve & Prozone
    • Assay Validation Parameters
    • Matrix interference

Bioanalytical Method Validation and Sample Analysis: "Common Problems"

  • Matrix Effect and Ion Suppression/Enhancement
    • Matrix Effect in Electrospray (ESI) LC-MS/MS
    • Remedy for Ionization Suppression in SPE-LC-ESI-MS/MS
    • Matrix Induced Ionization Suppression in APCI
    • Differential Suppression
      • The 3 Different Scenarios of Matrix Effect
      • Instrument Optimization to Reduce Matrix Effect
  • Carry-Over Guidelines
    • Impact of Carry-Over in Bioanalysis
    • Fighting Carry-Over
  • Drug Metabolism & Bioanalysis
    • Metabolite Conversion During Sample Extraction
    • Metabolite Conversion During Instrumental Analysis
    • General Strategy for Method using UV or Fluorescence Detection
    • General Strategy for Method using MS or MS/MS
    • Study Cases
  • Root Cause Analysis during Out of Specification investigation
    • Importance of Trend Analysis in GLP Bioanalysis

What's new in Bioanalysis?

  • The Purpose of the 3rd AAPS/FDA Bioanalytical Workshop
  • Crystal City III Conclusions
    • Quality Controls: Conventional and New Approaches
    • Evaluating Curve Models: Graphic & Mathematical Comparison
    • Factors Contributing to Imprecision and/or Inaccuracy
    • Carryover and Contamination Evaluation
      • Contamination criteria
    • Evaluate Contamination in Validation
    • Incurred Sample Re-Analysis (ISR)
      • Reproducibility of QC vs. Incurred Samples
      • Approach for ISR
    • Determination of Metabolites During Drug Development
    • Documentation Issues
    • Repeat Analyses
    • Matrix Effects for MS-Based Assays
    • Run Acceptance Criteria
    • Stability Recommendations
    • Autosampler Re-injection Reproducibility
    • Blood Stability
    • Method Evolution & Stability Measurements
    • Internal Standard Stability
    • Validation Topics with No Consensus:
      • -70oC vs. - 20oC
      • Reference Standard Expiration Date vs. Stock Stability
  • Other Validation tests
  • Analytical investigations
  • Pharmacokinetic repeats
  • Challenges in bioanalytical method development
  • Impact of metabolites on method development
  • Matrix Effects and Hemolysis Effect
  • Autosampler stability and re-injection reproducibility
  • Acceptance of nonlinear calibration models
  • Instruments/Techniques that Can Improve Quality in Regulated Bioanalysis
  • Concept Paper/ Recommendations on the Need for a Guideline on the Validation of Bioanalytical Methods
  • Metabolite Testing & MIST
  • Specificity in Presence of OTC Metabolites
  • Use of Variable Injection Volumes
  • Anticoagulants
    • Cross-Validation Between Different Anticoagulant Salt Forms

Bioanalysis Trends & Global Bioanalytical Outsourcing

  • Current Life Science Industry Trends:
    • Issues and Opportunities in the Pharmaceutical Industry
    • Reducing Cost and Faster Time-to-Market
  • Life Science Uncertainties:
    • Regulatory uncertainties
    • Scientific uncertainties
    • Intellectual Property (IP)
    • Commercial and financial
  • Challenges of Ageing Population:
    • Large increase in disorders of old age
    • Increasing unmet medical needs
  • Old Big Pharma model (closed development: internal capabilities) vs. the new Biopharma model (open development: outsourcing/partnership)
  • What is Driving Outsourcing for Pharmaceutical Companies?
  • Advantages in outsourcing: Reducing the number of compounds that fail in early trials
  • The FDA Amendment Act (FDAAA - Sep. 2007):
    • Current Prescription Drug User Fee Act (PDUFA IV)
    • FDAAA new mandates and impact for pharmaceutical companies
    • Title VIII Clinical trials database
    • Title IX - Post-market Drug Safety
  • Pharmaceutical Companies trend towards Global Outsourcing
  • North America & Europe vs. India & China
    • Why do Pharmaceutical companies turn to emerging markets?
    • India and China as an opportunity for Pharma companies to accelerate clinical development programs
    • R&D and Manufacturing costs abroad
    • Shortcomings and potential pitfalls of outsourcing in Asia
      • IP and legal protection
      • Uncertainties around quality
      • Different regulatory frameworks
      • Language and cultural differences

 

 

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