pharmaceutical analysis

Properties and Standards in Pharmaceutical Analysis

Properties of Chemical Reactions in Titration

  • Specific to the substances being analyzed.

  • Must be quantitative and fast (instantaneous).

  • Requires a 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. Good redox standard.

  • 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 and Agents

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: 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 Indicators and Chloride Determination

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.

Indirect Titration

When to Perform Indirect Titration

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

    • No suitable reaction.

    • Reaction may be too slow.

    • Volatile analyte.

Back Titration Procedure

  • Known quantity of a standard titrator solution is added in excess.

  • Allow reaction with the sample.

  • Determine excess by titration with another standard solution.

  • The difference indicates the amount reacted by the sample.

Non-Aqueous Titration

When to Perform Non-Aqueous Titration

  • Conducted using solvents other than water.

Role of Water in Acid/Base Titrations

  • Necessary for certain reactions, but non-aqueous solutions can extend the range of acids and bases measurable.

Targets for Non-Aqueous Titration

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

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

  • Compounds insoluble in water.