QC2 LEC PRELIM EXAM

• Analytical Chemistry is the area of chemistry responsible for the qualitative and quantitative characterization of the composition of matter
• Qualitative Analysis determines WHAT is present
• Quantitative Analysis determines HOW MUCH is present
• Terminologies:

  • RS refers to a USP Reference Standard
  • CS refers to Colorimetric Solution
  • TS refers to Test Solution
  • VS refers to Volumetric Solution
• "About" indicates a quantity within 10%
• "Negligible" indicates a quantity not exceeding 0.50mg
• "NLT" means not less than
• "NMT" means not more than
• Gas and solid measurements are in weight

  Liquid measurements are in volume

  Mixtures of solids and semi-solids are in %w/w

  Solutions or suspensions of solids in liquids are in %w/v

  Solutions of liquids and liquids are in %v/v
• Classification of Analysis by Sample Size:

  • Ultra micro: <1mg
  • Micro: 1mg-10mg
  • Semi-micro: 10mg-100mg
  • Macro: 100mg-1g
• Extent of Determination:

  • Proximate Analysis: Total amount of a group or class of compounds
  • Ultimate Analysis: Total amount of a specific compound
• Nature of Method:

  • Classical Method: based on chemical reactions (titrimetry, gravimetry)
  • Instrumental Method: based on physical/chemical properties of analysis (spectrophotometry, chromatography)
  • Special Method: for crude drugs, natural products (acid value, water/alcohol content)
• Quality of Analytical Method:

  • Accuracy vs Precision
  • Accuracy: nearness of the Experimental Value (EV) to the True Value (TV)
  • Precision: nearness of the EV to each other or togetherness
• Random Error is indeterminate, affects precision (standard deviation), and is difficult to eliminate

  Systematic Error is determinate, affects accuracy (mean), and can be:

  • Instrumental Error: caused by malfunctions in measuring devices or using the wrong grade of chemicals
  • Methodological Error: caused by deviations in the physical and chemical behavior of the reagents and reactions
  • Personal/Operative Error: caused by estimation of reading
• Quality Assurance of Pharmaceuticals:

  • Quality at low possible cost
  • Totality of characteristics or features of a product that bears on its capacity to satisfy stated or implied needs
  • Branded (Innovator) is more expensive compared to Generic
• Quality Relationships:

  • Quality Management: aspect of management function that defines the "quality policy" and overall intentions and direction relating to the quality of SOP management
  • Good Manufacturing Processes (GMP): ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use, concerned with both production and QC
• Important Documents:

  • Monograph: specifies all the tests to be conducted on a product and/or appropriate references containing details of the procedure
  • Certificate of Analysis (COA): document with the results of all tests conducted to show compliance or non-compliance
  • Standard Operating Procedures: details the reasons behind a procedure and the proper sequence of steps to be done
• 4 Types of QC Tests:

  • Raw Material Quality Control
  • In-process Quality Control
  • Finished Product Quality Control
  • Packaging Material Quality Control
• Raw Material Quality Control includes:

  • Identification
  • Purity
  • Limit
  • Physical
  • SPECIAL Identification Tests
• Methods under Identified Tests:

  • Chemical methods
  • Instrumental methods (IR Spectroscopy, UV/Vis Spectroscopy, High Performance Liquid Chromatography, Nuclear Magnetic Resonance)
• Limit Tests process impurities, synthetic by-products, and other inorganic and organic impurities that may be present in the drug substances and excipients used in the manufacture of the drug product
• Physical Tests include:

  • Specific Gravity
  • Solubility Test
  • Refractive Index
  • Optical Activity
  • BP - MP
• Special Tests for specific substances like Paracetamol, Aspirin, and Quinidine sulfate
• In-process Quality Control for Powders and Granules and Tablets
• Powders and Granules In-process Quality Control includes:

  • Uniformity of Mixture
  • Initial Moisture Content
  • Adequacy of Wetness
  • Final Moisture Content
  • Particle Size Distribution
  • Bulk and Tapped Density
  • Powder Flow
• Tablets In-process Quality Control includes:

  • Tablet Crushing Strength/Hardness
  • Thickness
  • Weight Tolerance
  • Friability
• Methods for determining Tablet Crushing Strength include Stokes Monsanto, Strong Cobb Hardness Tester, Pfizer Hardness Tester, Eureka Hardness Tester, and Schleuniger Hardness Tester
• Thickness is measured using a Micrometer Caliper with acceptance criteria of ≤5% RSD
• Weight Variation Tolerance criteria depend on the average weight of the tablets
• Acceptance Criteria for weight variation and number of tablets outside the acceptable weight variation