QC1

• Types of chemical reactions which serve as the basis of titrimetric analysis

  • Oxidation - Reduction
  • Neutralization
  • Precipitation
  • Complexation
• Each type of chemical reaction is used extensively for analysis of drugs and dosage forms official in the USP and NF
• Ways reactions may be made to go to completion

  • Formation of a slightly dissociated substance as a reaction product
  • Removal of one or more of the products of the reaction as a gas
  • Removal of an ionic substance such as a complex ion
  • Adding an excess of one of the reactants
• Neutralization reactions


  Chemical reactions or chemical processes in which an acid (proton donor) reacts with a base (proton acceptor)
• Products of neutralization reactions

  Salt and water
• Indicators


  Complex organic compounds used to determine the endpoint in neutralization process, determine hydrogen ion concentration [H+] or pH, and indicate that a desired change in pH has been affected
• Types of indicators


  • pH indicator
  • Acid - base indicators
• Theories explaining the color change of indicators

  • Physicochemical theory: attributes the color to certain ions
  • Organic theory: attributes the color to certain groupings of the elements in a compound
  • Colloidal theory: assumes that indicators form colloidal solutions and the change in color is dependent upon a change in size of the colloidal particle
• Rules in using indicators

  • Use 3 drops of indicator test solution for a titration unless otherwise stated
  • Strong Acid + Strong Base: Methyl Red, Methyl Orange, Phenolphthalein
  • Weak acid + Strong Base: Phenolphthalein
  • Weak alkali + Strong Acid: Methyl Red
  • Weak acid + weak base: NEVER titrate = since no indicator will give a sharp endpoint
• Commonly used pH indicators

  • Methyl Yellow
  • Methyl Orange
  • Methyl Red
  • Bromophenol Blue
  • Bromocresol Purple
  • Bromothymol Blue
  • Phenolphthalein
  • Bromocresol Green
• Acidimetry


  Titration of bases with a standard acid, analysis of base
• Aqueous volumetric standards


  • HCl, H2SO4
• Non-aqueous volumetric standards


  • Perchloric acid in glacial acetic acid
• Aqueous primary standards


  • Anhydrous sodium carbonate
• Non-aqueous primary standards


  • Potassium bipthalate
• Aqueous secondary standards


  • NaOH
• Aqueous direct titration


  • NaOH, KOH, Na2CO3, NaHCO3, Na Salicylate
• Non-aqueous direct titration


  • Methacholine Chloride
• Aqueous residual titration


  • ZnO, Milk of magnesia, Na K Tartrate, Methenamine
• Aqueous indicators for weak bases (salts)


  • Crystal violet, Malachite green, Methylrosaniline chloride, Quinoline red, Alpha-naphthol benzene
• Aqueous indicators for stronger bases

  • Methyl red, Methyl orange, Thymol blue
• Non-aqueous titrations are used for weakly basic substances such as amines, amine salts, heterocylic nitrogen compounds, alkali salts of organic acids, alkali salts of weak inorganic acids, and amino acids
• Kjeldahl method


  Assay of nitrogen content, where an equivalent amount of ammonia can be obtained as ammonium sulfate by digestion of the sample with concentrated sulfuric acid until decomposition is complete
• Some alkaloids and other nitrogen-containing organic compounds fail to yield all of their nitrogen upon digestion with sulfuric acid, so the Kjeldahl method cannot be used for the determination of nitrogen in all organic compounds
• The Kjeldahl method is done if the ammonia is not quantitatively liberated from an organic nitrogen containing compound by acid or alkaline hydrolysis
• Nitrogen in Kjeldahl method

  Trivalent state, amino or amido nitrogen
• Kjeldahl method


  1. Digestion of the sample with concentrated sulfuric acid until decomposition is complete

  2. Ammonia is liberated by treatment of the residue of ammonium sulfate and excess sulfuric acid with sodium hydroxide

  3. Ammonia is distilled into excess boric acid

  4. The distillate is titrated in the usual manner
• Ways to reduce time of digestion in Kjeldahl method

  • Addition of potassium sulfate or anhydrous sodium sulfate (increase temperature)
  • Addition of catalysts: Copper sulfate or Selenium
• If all or part of the nitrogen is present as nitrate in the Kjeldahl method, further modification is necessary such as addition of salicylic acid to the digestion mixture and addition of sodium thiosulfate
• Kjeldahl method 1 (macro method)

  Ammonia is distilled into excess boric acid solution using a 500mL Kjeldahl flask
• Kjeldahl method 2 (semi micro method)


  Smaller samples employed using a semi micro Kjeldahl apparatus, with quantity of material equivalent to 2 to 3 mg of nitrogen
• Alkalimetry


  Titration of acids with a standard base, analysis of acids
• Aqueous volumetric solutions


  • NaOH, KOH, Ba(OH)2
• Non-aqueous volumetric solutions


  • Na methoxide, Lithium methoxide, K methoxide
• Aqueous primary standards


  • K biphthalate
• Non-aqueous primary standards


  • Benzoic acid in dimethyl formamide
• Aqueous secondary standards


  • HCl, H2SO4
• Aqueous direct titration


  • HCl, Diluted phosphoric acid, Tartaric acid, Boric acid, citric acid
• Non-aqueous direct titration


  • Phenytoin, Barbiturates
• Aqueous residual titration


  • Esters, Acid anhydrides, Acid chlorides, Aldehydes, Aspirin, Formaldehyde, Parabens, Chloral hydrates