Lecture 01

• What is the focus of impurity testing in drug manufacture?

  Understanding the origin of related impurities
• Where can impurity testing methods be found?

  In the British Pharmacopoeia
• Why is it important to choose methods for impurity testing?

  To ensure accurate detection of impurities
• What does 'analyte' refer to in analytical chemistry?

  The substance being identified and measured
• What is a 'sample' in the context of analytical chemistry?

  The stuff which should be analysed
• What is a 'standard' in analytical chemistry?

  A sample with a known concentration of analyte
• What does 'matrix' refer to in a sample?

  Other ingredients than the analyte in a sample
• What is 'calibration' in analytical chemistry?

  A correlation between analytical signal and analyte concentration
• What is 'certified reference material'?

  A sample tested by independent expert laboratories
• What are the central ideas of analytical chemistry?

  • Qualitative analysis: reveals identity of analyte
  • Quantitative analysis: reveals amount or concentration of analyte
• What is the flow of chemical analysis?

  1. Define the problem
  2. Define the method used
  3. Take samples
  4. Process samples
  5. Prepare standards
  6. Measure standards and samples
  7. Evaluate results (QC/QA)
  8. Apply statistics
  9. Present results
• What should be considered when defining the problem in analytical chemistry?

  Qualitative or quantitative analysis needed
• What is acid digestion in impurity analysis?

  Aqua regia is used to digest samples
• What are common contaminants in Active Pharmaceutical Ingredients (API)?

  • Solvents
  • Reagents
  • Metals from catalysts, salts, equipment
  • Random impurities from poorly cleaned equipment
  • Reaction by-products related to API
  • Starting materials related to API
• Why are related impurities in API significant?

  They can affect drug efficacy and toxicity
• What is required for testing impurities in API?

  They need to be tested as part of a specification
• What is the significance of the synthesis of Paracetamol?

  It illustrates potential issues in drug synthesis
• What can go wrong in the first step of Paracetamol synthesis?

  Starting materials or reagents may be impure
• What is the purpose of NMR in drug synthesis?

  To check the final product for purity
• What is the acceptable limit for impurities in drug products?

  They must meet specifications set for related impurities
• What are the objectives in testing drug products?

  • Identity testing of the product
  • Ensuring product cleanliness
  • Assay of the product
  • Understanding expected impurities
• What types of impurities can be expected in an API?

  Water, metals, salts, solvents, reagents
• How can impurities affect the product?

  They may be toxic or cause instability
• What is the significance of limits for impurities in the BP monograph?

  They provide guidelines for acceptable impurity levels
• What are the sources of related impurities in formulated products?

  • From excipients
  • From impure API
  • From reactions of API with excipients
  • From reactive impurities related to API
• What is HPLC used for in impurity analysis?

  It separates components for quantification
• What does the peak size in HPLC indicate?

  It is proportional to the amount of analyte
• What are the features of an HPLC chromatogram?

  • Time on X-axis, absorbance on Y-axis
  • Peaks labelled with retention time
  • Specific peaks for each impurity
• Why is good separation of peaks necessary in HPLC?

  To accurately quantify each impurity
• What factors can affect HPLC method development?

  • Varying the pH of the mobile phase
  • Adjusting the flow rate
  • Changing the column temperature