Analysis

• Volumetric analysis


  One of the classical methods of analysis involving measurement of reacting volumes and mass of substances in aqueous or non-aqueous solution/solvents
• Requirements for Volumetric Analysis

  • Reaction should be simple & expressed by a well-defined chemical equation
  • Reaction should be rapid
  • Reaction must proceed to completion when an equivalent amount of standard solution has been added
  • There must be some sharp change in either physical or chemical properties of the solution at the equivalence point (end-point)
  • Reaction should have some simple method for the detection of end point or equivalence point of titration
• Titrant


  Solution contained in the burette and which is added to the analyte
• Titrand


  Sample solution whose volume is measured by pipette or the analyte solution
• Titre


  Volume of solution needed to reach the end-point in a titration
• Volumetric titrations


  Involve measuring the volume of a solution of known concentration that is needed to react completely with the analyte
• Analyte


  Substance or chemical constituent that is determined in an analytical procedure
• Indicator


  Substance used to determine the end in titration
• Titration


  Technique of slowly adding a standard solution from a burette to a solution of the analyte until the reaction between the two is judged complete
• Direct titration


  Type of titration whereby a known concentration and volume of the titrant is added to the substance in order to analyze it
• Indirect titration


  Also referred to back titration, involves reacting an analyte with excess of a standard solution and then titrating the excess amount of the standard solution with a second standard solution to determine the analyte concentration
• Blank titration


  Titration without an analyte being present, only the solvent used in the analyte solution preparation
• Quantitative transfer


  Transfer of a sample from one container or vessel to another such that none is lost
• Equivalence Point


  Point in a titration when the amount of added standard reagent is equivalent to the amount of analyte
• End-Point


  Point at which the distinguished color change occurs in titration
• Titration error


  Difference in values between practical and theoretical end point
• Accuracy


  Degree of agreement between the measured value and the true value
• Precision


  Degree of agreement between replicate measurements of the same quantity, i.e. the repeatability of a result
• Causes of Titration Errors

  • Errors in measurements of volumes and masses of reacting substances
  • Indicator error - indicators can take part in the reaction
  • Random errors - committed during and after experiment, vary from one person to another
• Equivalent (equiv)


  Number of gram-equivalents involved in a quantitative method
• Milliequivalent (meq)


  Number of gram-milliequivalents involved in a quantitative method
• Gram Equivalent (Equivalent weight)


  Weight of an acid, base or salt that contains 1 gram of replaceable hydrogen, hydroxyl group or cation/anion
• Gram-equivalent Weight (GEW)

  Weight in grams that is chemically equivalent to 1 gram-atom of hydrogen (1.0079 g)
• Impurities in pharmaceuticals


  Unwanted substances that remain with the active pharmaceutical ingredients (APIs), or develop during formulation, or upon aging of pharmaceutical products
• Sources of impurities in pharmaceuticals

  • Raw materials
  • Intermediates
  • Reagents
  • Catalysts
  • Solvents
  • Reaction vessels
  • Contamination due to improper storage
• Effects of impurities in pharmaceuticals

  • They lead to cumulative toxic effect
  • Can cause accelerate degradation of the product
  • May influence the efficacy of the pharmaceutical products
• Classification of impurities in pharmaceuticals

  • Synthesis related impurities
  • Formulation related impurities
  • Environmental related impurities
  • Impurities on aging
• Synthesis related impurities


  • Organic impurities (e.g. by-products, degradation products and chiral impurities)
  • Inorganic impurities (derived from the manufacturing processes used for bulk drugs, normally known and identified)
  • Residual solvents (can change properties or be harmful)
• Formulation related impurities


  • Dosage form related impurities (e.g. liquid dosage form precipitation of main ingredient due to various environmental factors)
  • Method related impurities (arise from preparation method and sterilization conditions)
• Environmental related impurities


  • Temperature (can degrade thermolabile compounds)
  • Photolytic degradation (from UV/visible light exposure)
  • Humidity (affects stability of bulk powder and formulated solid dosage forms)
• Impurities on aging


  • Packaging material (impurities may leach from glass, rubber, plastic)
  • Leaching (oxides like NO2, SiO2, MgO leached from glass into product)
• Methods of control of impurities

  • Limit tests
  • Spectroscopic techniques
  • Chromatographic techniques
• Limit tests


  Qualitative tests designed to identify and control small quantities of inorganic impurities
• Factors to consider in limit tests

  • Specificity of the tests (selective reaction with trace impurity)
  • Sensitivity (to impurity concentration)
  • Control of personal errors (exclude ambiguity)
• Quantitative determinations


  • Limits of insoluble matter
  • Limits of soluble matter
  • Limit of moisture, volatile matter, and residual solvents
  • Limits of non-volatile matter
  • Limits of residue on ignition
  • Loss on ignition
  • Ash values
• Assay


  Quantitative test
• Limit test


  Semi-quantitative or qualitative test for range of impurities
• A free radical is an atom, molecule, or ion that has at least one unpaired valence electron
• Limit test for chlorides

  1. Dissolve sample in water

  2. Add dilute nitric acid

  3. Add silver nitrate

  4. Stir and allow to stand

  5. Compare opalescence to standard
• Limit test for sulphates

  1. Take sample solution

  2. Add dilute hydrochloric acid

  3. Dilute to 45 ml

  4. Add barium sulphate reagent

  5. Keep aside for 5 min

  6. Observe turbidity