ACIDIMETRY

• Acidimetric Analysis
• Activities

  1. Explaining the principles of acidimetric method of analysis

  2. Applying acidimetric-titrimetric techniques in analysis of drug and drug products
• Acidimetric analysis


  The direct or residual titrimetric analysis of bases using an accurately measured volume of acid, is supplied in the analytical control of a considerable number of both official inorganic and organic substances
• Direct titration


  1. Conducted by introducing a standard acid solution gradually from a buret into a solution of the base being assayed until chemically equivalent amount of each have reacted as shown by some change in properties of the mixture

  2. An endpoint which must be close to stoichiometric point is made evident by a change in the color of some indicator or by potentiometric means
• Residual titration


  Also known as BACK TITRATION, used whenever the end point of a direct titration deviates appreciably from the stoichiometric points for some reason, e.g. when the basic sample is insoluble in water and rate of its reaction with the standard acid is relatively slow, or when the substance to be assayed does not give a distinct, sharp end point with an indicator by direct titration
• DIRECT TITRATION METHOD

  1. ASSAY OF SODIUM BICARBONATE

  2. Analyte – 3g NaHCO3 + 25mL water + Methyl orange TS

  3. Titrant – 1N H2SO4

  4. Chemical Reaction: 2NaHCO3 + H2SO4
• Methyl orange


  Used as indicator because most other indicators are affected by the carbonic acid liberated in the reaction, which causes a change in color before the reaction is complete
• Meqwt


  = MW /f x 1000
• Factors

  • Based on the number of replaceable H+, number of replaceable OH-, and valence of cation
• Factors

  • H+ - HCl = 1
  • H2SO4 = 2
  • H3PO4 = 3
  • OH- - NaOH – 1
  • Ca(OH)2 = 2
  • Al(OH)3 = 3
• Sample Problem 1

  If exactly 3.0g of NaHCO3 is titrated in 25 ml of H2SO4 what will be the N of the solution? MW 84
• USP Standard: not less than 99.0 and not more than 100.5 %
• Sample Problem 2


  If a 0.2800 – g sample of sodium bicarbonate (96.5%NaHCO3) is titrated with 0.9165N sulfuric acid, what is volume of the acid should be required to produce an end point?
• Substances/Compounds assayed by Direct Acidimetric analysis

  • Assay of NaHCO3
  • Assay of NaOH
  • Assay of Sodium salicylate Tablets
• RESIDUAL TITRATION METHOD

  1. ASSAY OF ZINC OXIDE

  2. Freshly ignited zinc oxide, contains not less than 99% and not more than 100.5% of ZnO

  3. Methyl orange indicator

  4. Titrant – 1N H2SO4 and 1N NaOH

  5. Residual titration is carried out by dissolving the analyte in an accurately measured quantity of VS known to be in excess and titrating the excess of the latter with another standard solution
• Equivalent weight (EW)


  = MW/valence
• The equivalent weight of ZnO is 40.68g, therefore each mL of 1N H2SO4. 1 mEq neutralized by ZnO is equivalent to 40.68 mg
• Sample Problem 3

  Calculate the titer value of 1N H2SO4 for ZnO.

  2. If 1.2 g of ZnO, were treated with 50 mL of 1.1230N sulfuric acid, and 27.6 mL of 0.9765N NaOH were required in the back titration. Calculate the %ZnO in the sample
• Titer value = MW/Valence x conc. = 81.38/2 x 1N = 40.69 mg
• Residual Titration Method for Assay of Milk of Magnesia

  1. Milk of magnesia Mg(OH)2 is dissolved in accurately measured excess of 1N sulfuric acid solution

  2. Complete neutralization of all the magnesium hydroxide with the formation of the soluble magnesium sulfate

  3. Methyl red indicator used
• U.S.P. requires that milk of magnesia contain not less than 7% and not more than 8.5% Mg(OH)2
• Sample Problems

  • 5.2430g sample of magnesia magma dissolved in 25ml of 0.9915N H2SO4 required 9.85ml of 1.1402N NaOH to titrate the excess acid
  • 12.32 g of milk of magnesia dissolved in 50 ml of 1.0340N sulfuric acid, producing a mixture that required 24.60ml of 1.1255 N NaOH
• Substances/Compounds assayed by residual Acidimetric analysis

  • Milk of Magnesia
  • Methenamine
  • Ammonium chloride Injection
• Nitrogen Determination by the Kjeldahl Method

  1. Method I - macromethod, ammonia distilled into excess boric acid

  2. Method II - semi-micro method, smaller samples, nitrogen liberated by acid digestion
• Kjeldahl Method

  • Developed by Johann Kjeldahl in 1883
  • Strong acid helps in the digestion of food to release nitrogen which can be determined by titration
• Kjeldahl Method Problems

  • 6.20g sample of organic nitrogen compound, ammonia distilled into 50ml of 0.1248N sulfuric acid, titrated with 22.45 ml of 0.0965N NaOH
  • 256μL of solution containing 37.9 mg protein/mL, ammonia collected in 5 mL of 0.0336 M HCl, remaining acid titrated with 6.34 mL of 0.010 M NaOH
• Molecular weight of nitrogen is 14
• References

  • Watson, David G. Pharmaceuticals analysis: a textbook for pharmacy students and pharmaceutical chemists, 4th ed. Singapore: Elsevier. 2017.
  • Knevel, A.M. and Digangi, F.E., Jenkin's Quantitative Pharmaceutical Chemistry.USA: Mc Graw Hill. 1977.
  • Handbook of Modern Pharmaceutical Analysis (2011) Amsterdam; Boston: Academic Press/Elsevier
  • How to do a titration and Calculate the concentration https://www.youtube.com/watch?v=2VQM8suez8U