Pharmaceutical Analysis 1 – Module 4

• Precipitimetry


  Precipitation Titrimetric Analysis - Based on the formation of relatively insoluble substances (precipitates) to cause the reaction to go to completion quantitatively
• Argentometry


  If the titrant used is AgNO3 standard solution
• Halides


  • Cl-
  • Br-
  • I-
  • F-
• Endpoint determination methods


  • Cessation of precipitation or appearance of turbidity
  • Use of internal indicators
  • Instrumental methods (potentiometry/amperometry)
• Ferric Ammonium Sulfate (ferric alum)


  Used as indicator in direct and residual titration, endpoint is white (AgSCN) to reddish brown complex (FeSCN2+)
• Potassium Chromate


  Used as indicator, endpoint is red precipitate (Silver chromate) against the white background of AgCl
• Adsorption indicators


  • Examples: Dichlorofluorescein (DCF), Eosin Y, Tetrabromophenolphthalein ethyl ester (TEE)
  • Used in analysis of halides by direct titration with AgNO3
  • Are weak acids
  • Endpoint best seen in diffused-light condition
• Fajans method


  • Direct titration using AgNO3 as titrant
  • Uses an adsorption indicator that adsorbs onto or desorbs from the surface of the solid
  • Rapid, accurate, and reliable
• Volhard method


  • A form of residual or back-titration
  • Complete precipitation of insoluble silver salts with the addition of excess silver nitrate
  • Followed by titration of the unreacted silver nitrate with ammonium thiocyanate
  • Ferric alum as indicator (reddish-brown endpoint)
• Mohr method


  • Potassium chromate serves as the indicator for the argentometric titration of neutral halides
  • 2Ag+ + CrO4-2 → Ag2CrO4 (brick red)
  • Rarely used because Cr(VI) is a carcinogen
• Precipitation, Complexation and Redox Titration Methods

  • Fajans (Direct, Adsorption Indicators, AgNO3 as titrant, Colored ppt endpoint)
  • Volhard (Residual, Ferric Ammonium Sulfate (ferric alum) indicator, NH4SCN, Reddish brown complex endpoint)
  • Mohr (Direct, Potassium Chromate indicator, Seldom used-carcinogenic, Red ppt endpoint)
• Example Applications


  • Assay of Phenylmercuric Nitrate for Mercury Content
  • Assay of Iopanoic Acid Tablets
  • Assay of Benzyltrimethyammonium Chloride
  • Assay of Sodium Chloride
  • Assay of Iodide Content in Povidone Iodine
  • Assay of Sodium Lauryl Sulfate for Sodium Chloride Content
• Sodium Tetraphenylboron Titrations


  • Uses Na(C6H5)4B to precipitate organic nitrogen compounds, ammonium, potassium, and silver ions
  • Uses chloroform as extraction indicator, endpoint is colorless
• Complexometry


  Complexation Titrimetric Analysis - Metal ion reacts with a suitable ligand to form a complex, and the end point is determined by an indicator or an appropriate instrumental method
• EDTA


  Ethylenediaminetetraacetic acid, most widely used titrant, available as dihydrate of sodium salt, a hexadentate ligand, commonly used in 0.05 M concentration
• EDTA forms 1:1 ratio with metals, regardless of charge
• Masking


  Control over interferences in EDTA titrations, can be done by pH regulation or addition of masking agents (auxiliary ligands that preferentially form highly stable complexes with potential interfering ions)
• Examples of Masking Agents

  • Triethanolamine
  • Thioglycols
  • Ammonium Fluoride
  • Ascorbic acid, citrates and tartrates
• EDTA Titration Indicators


  • HNB, eriochrome black T, azo dyes, phthaleins
  • Qualities: sharpness of color change, stability for metal ion, stability constant smaller than metal-EDTA complex
• Types of EDTA Titrations

  • Direct (Ca+2, Mg+2, Zn+2)
  • Residual (Al, Bi compounds - back-titrant: ZnSO4, indicator: dithiozone, solvent: organic/alcohol)
• Ferric Chloride Titration


  For sodium fluoride determination, titrant: FeCl3 TS, indicator: KSCN, endpoint: red color
• Water Hardness


  • Capacity of cations in water to form sparingly soluble products, expressed as CaCO3 or Ca content
  • Types: Temporary (due to bicarbonates) and Permanent (due to chlorides and sulfates)
• Atoms and ions have 3 subatomic particles: protons, neutrons, electrons
• Cation


  Positively charged ion
• Cation formation


  Due to loss of electrons, becoming positively charged
• The net charge of an atom is generally neutral/zero
• Cation


  A positively charged ion
• Anion


  A negatively charged ion
• Gegenion


  A counterion
• Zwitterion


  A bipolar ion
• Cations are formed due to

  Loss of electrons, becoming positively charged
• Anions are formed due to

  Gain of electrons, becoming negatively charged
• An atom is composed of

  • Proton (+)
  • Neutron
  • Electron (-)
• Atom loses electron


  Valence/charge increases
• Atom gains electron


  Valence/charge decreases
• Oxidation-Reduction (Redox) Reactions


  Electrons are transferred from one reactant to another
• Oxidation


  Valence increase due to loss of electrons
• Reduction


  Valence decrease due to gain of electrons
• In the given reaction, Cu(s) is the Reducing Agent
• Identify the oxidizing and reducing agents in the reactants of the reaction

  1. Determine the valence change

  2. Determine the loss or gain of electrons