pharmaceutical analysis

Properties of Chemical Reactions in Titration:

• Specific to the substances being analyzed.

• quantitative

• fast (instantaneous).

• suitable indicator to show when the reaction is complete.

• Referenced to a suitable standard.

Choosing an Indicator

• Must show a visible response (color change) when the reaction reaches an endpoint.

• Should change color at the equivalence point to minimize titration error.

Primary Standard Requirements

• Very high purity.

• Easily tested for impurities.

• Heat stable.

• Non-reactive with air, water, and CO2.

• High molar mass to minimize weighing errors.

• Soluble in the solvent used in titration (commonly water).

Uses of Primary Standards

• Benzoic Acid: Acts as a standard acid; low solubility in water. .

• Potassium Iodate: Standard for redox reactions.

• Anhydrous Sodium Carbonate: Acts as a standard base, absorbs water and CO2 from the atmosphere.

• Sodium Chloride: Standardizes silver nitrate solutions.

• Zinc: Standardizes EDTA solutions.

Titration Reactions

• Acid-base (neutralization).

• Redox.

• Complex formation.

• Precipitation.

Choosing Acid-Base Indicators

• Chosen to ensure color change occurs near the equivalence point.

• Typically weak organic acids with color differences in ionized states.

Common Oxidizing Agent

• KMnO4: Used in acidic medium. Color change from pink to deep purple.

Common Reducing Agent

• Thiosulfate: Used in iodine reactions. Iodine's color indicates the endpoint; starch is added for sharper detection.

Common Standard Complexing Agent

• EDTA: Forms 1:1 complexes with metal ions. Polydentate ligand, forms chelate complexes.

Medium Requirements for Complexometric Titration

• pH must be constant, often maintained using an alkaline buffer.

• Metal stability depends on pH; excess H+ can compete with metal ions for the ligand.

• Disodium edetate is commonly used due to higher solubility.

Properties of Metal Indicators

• Form 1:1 complexes that are weaker than EDTA.

• Should not compete with EDTA, and the indicator color must differ from the metal indicator complex.

Determining Halide Concentration

• Silver Nitrate and Halide Ions: Method primarily used for chlorine determination. A reverse procedure can be applied, e.g., Ag+ + Cl- → AgCl.

When to Perform Indirect/back Titration:

• Preferred when many substances cannot be titrated directly due to:

  • No suitable reaction.

  • Reaction may be too slow.

  • Volatile analyte.

When to Perform Non-Aqueous Titration:

• Conducted using solvents other than water.

Targets for Non-Aqueous Titration

• Very weak acids (e.g., phenolic compounds).

• Very weak bases (e.g., organic amines).

• Compounds insoluble in water.