Introduction to Pharmaceutical Analysis

Pharmaceutical analysis is a branch of chemistry, which involves a series of processes for the identification, determination, quantitation, and purification. This is mainly used for the separation of the components from the mixture and for the determination of the structure of the compounds. The different pharmaceutical agents are as follows:

  1. Plants
  2. Microorganisms
  3. Minerals
  4. Synthetic compounds

Based upon the determination type, there are mainly two types of analytical methods. They are as follows:

  1. Qualitative analysis: This method is used for the identification of the chemical compounds.
  2. Quantitative analysis: This method is used for the determination of the amount of the sample.

Types of Analytical Methods

Analytical methods are mainly of the following two types:

1.   Classical methods Methods of Analysis:

  1. Gravimetry—the weight of the sample is determined after the precipitation.
  2. Titrimetry—the volume of the solution is determined after the reaction such as neutralization, complex formation, precipitate formation, and oxidation and reduction.
  3. Volumetry—the volume of the gas evolved by the reaction is determined.

2.   Instrumental Methods of Analysis:

  1. Electrochemical methods—used for the measurement of the current, voltage, or resistance. Examples
1. Conductometry—measurement of the conductance
2. Potentiometry—measurement of the potential
3. Coulometry—measurement of the current
4. Voltammetry—measurement of the current at a specified voltage

2. Optical methods—based upon the measurement of radiation absorbed or emitted.

Examples:Absorption methods—visible, Ultraviolet (UV), Infrared (IR), Atomic Absorption
 Emission methods—plasma emission spectroscopy, flame spectroscopy, and fluorimetry

3. Chromatography—Paper Chromatography, High-Pressure Liquid Chromatography (HPLC), Gas Chromatography (GC), ion exchange, Thin Layer Chromatography (TLC), and column chromatography.

4. Thermal methods—Differential Thermal Analysis (DTA), Thermogravimetric (TG), and Differential Scanning  Calorimetry (DSC)

5. Other methods—X-ray diffractometry, radioactive methods, mass spectrometry, refractometry and polarimetry.

Factors Affecting the Analytical Methods Selection

  1. Type of the analysis whether it is elemental or molecular or atomic or the other.
  2. Nature of the material.
  3. The precision and accuracy required for the analysis of the sample.
  4. The time available for the analysis of the sample.
  5. The concentration range of the sample.
  6. Availability of the standard for the sample.

Introduction to Titrimetry

Titrimetry is the volumetric procedure for the determination of concentration of the sample by the addition of the known concentration or volume of the standard substance. This reacts quantitatively with the sample solution. Then a chemical  substance is used to detect  the end point by the colour change or by the precipitate or complex formation at the equivalent point of the titration. This substance is known as the indicator.

The following are the general terms used in the titrimetry:

  1. Titrant: This is a solution of the known concentration of the standard substance, which is added to the sample solution from the burette.
  2. Titrand: This is a solution of the unknown sample whose concentration is to be determined.
  3. Equivalence point: This is a point where the reaction between the titrant and titrand are completed and it can be detected by the colour change of the indicator.

Types of Titrations

The types of titrations can be classified based on the following:

I.   Based on the measurement:

VolumetryGravimetry
measurement of the volume of the titrantmeasurement of the weight of the titrant
  1. Volumetry: This is nothing but the measurement of the volume of the titrant required to complete the reaction.
  2. Gravimetry: This is nothing but the measurement of the weight of the titrant required to complete the reaction.

II.    Based on the nature of the titrant used:

  1. Aqueous titrations: These titrations are based upon the titration of the sample solution by using aqueous titrants such as hydrochloric acid and sodium hydroxide.
  2. Non-aqueous titrations: These titrations are based upon the titration of the sample by using non-aqueous titrants such as dimethylformamide.

III.    Based on the principle of titration:

A. Acid-base titrations: These titrations are based upon the titrations of the acidic or basic compounds by the consequent acids or bases. These reactions are mainly based upon the reactions of the hydrogen ion and hydroxide ion to form water.

Examples:Titration of HCl with the NaOH
 Titration of the KOH with the HCl

Here, any free base or acid is neutralized by its subsequent acid or base.

Based on the acid or base to be neutralized, again these reactions are classified into the following two sub classes:

  1. Acidimetry: Titration of free bases or salts of weak acids with a strong acid. Example: Titration of strong base (NaOH)  with acid (HCl)
  2. Alkalimetry: Titration of free acids or salts of weak bases with a strong base.

Applications of acidimetry and alkalimetry are as follows:

  • Alkalinity determination in water
  • Determination of acid content in wine or fruit juice.
  • Determination of acid content in milk.
  • Determination of Total Acid Number (TAN) and Total Base Number (TBN) in petroleum products, edible or inedible oils and fats.
  • Determination of boric acid in cooling fluids of nuclear power stations.
  • Determination of free or total acidity in plating baths.
  • Determination of active ingredients in drugs or raw materials for the pharmaceutical industry.
  • Total nitrogen determination using the Kjeldahl technique.

B. Oxidation-reduction titrations: These reactions are mainly based upon the oxidation-reduction reactions by using oxidizing  or reducing  agents.Example:

Permanganate titrations—these reactions are commonly known as redox reactions. By name itself it indicates the change of the oxidation state or transfer of electrons of the reactants by the use of oxidizing or reducing agents.

Oxidizing agents: Iodine, potassium dichromate, potassium permanganate solutions, Cerium IV salts, hydrogen peroxide, oxidized chlorine, for example, ClO , ClO .

Reducing agents: Sodium thiosulphate solutions, oxalic acid, ammonium iron (II) sulfate (Mohr’s salt), hydrogen peroxide, phenyl arsine oxide (PAO).

Applications of redox titrations are as follows:

  1. Determination of Chemical Oxygen Demand (COD) of water.
  2. Determination of oxidation capacity of water by permanganate.
  3. Determination of free and total SO2 in water, wine, alcohol, dried fruit, etc.
  4. Vitamin C determination.
  5. Titration of copper or tin using iodine.
  6. Titration of chromium VI.
  7. Determination of water in hydrocarbons.

IV. Complexometric titrations:

These titrations are mainly based upon the complexation reactions by using the complexing agent such as the titrant.

Example: EDTA titrations—these reactions are carried out by complex formation by combining ions by using complexing agents like Ethylenediaminetetraacetic Acid commonly known as EDTA. The endpoint is detected by using metal ion detectors.

Applications of complexometric titrations are as follows:

  1. Total hardness of water (Ca and Mg).
  2. Determination of Cu, Ni, Pb, and Zn in plating baths.
  3. Determination of Ca and Mg.

V.Precipitation titrations:

These titrations are mainly based upon the precipitate formation by using the precipitating agents.

Example: AgCl titrations—these reactions are carried out by the formation of precipitate by combining the ions by using the precipitating reagents.

Applications of precipitation titrations are as follows:

  1. Determination of chloride in water.
  2. Determination of chloride in many finished products (cooked meats, preserves, etc.).
  3. Determination of chloride in dairy products.
  4. Determination of silver in various alloys (for jewellery).
  5. Titration of halides.

VI. Non-aqueous titrations

These titrations are mainly based upon the titrations by using the non-aqueous titrants.

Example: Titrations using perchloric  acid and sodium methoxide.

Conditions Required for the Titrimetric Analysis

  1. The reaction should be simple, which can be easily expressed by a simple chemical equation. Example: Titration of NaOH with HCl which can be expressed by a simple equation.
  2. The titration should be relatively fast.
  3. The endpoint should be detected by physical or chemical change.
Examples:Colour change
 Precipitate formation
 Complex formation

Standard Solution:

This contains the known weight of the reagent in a definite volume of the solution, which has the standard concentration. The concentration is expressed by the following terms:

  • Formality (F): The number moles of solute per litre of solution with regardless to the chemical formula of the compound.
  • Molarity (M): The number of moles of solute per litre of solution with regard to chemical formula of the compound.
  • Molality (m): The number of moles of the solute in 1 Kg of the solution.
  • Normality (N): The number of equivalents of the solute in 1 litre of the solution.
  • Equivalent weight (EW): The weight of the one equivalent compound.

The following standard solutions are used in the titrations:

Primary standard:

This is the pure form of the substance with equivalent weight.

Examples of Primary standardPotassium hydrogen phthalate
 Succinic acid
 Sodium carbonate
 EDTA

The primary standard should have the following requirements:

  1. It should be stable.
  2. It should be completely soluble in the solvent.
  3. Its purity can be determined by the standard analytical methods.
  4. The reaction with the standard solution should be stoichiometric reactions

Secondary standard:

This is a solution, which is previously standardized by the titrating with the primary standard.

Examples of Sec. standardsSodium thiosulphate
 Oxalic acid
 Copper sulphate

The secondary standard should have the following requirements:

  1. The concentration of the secondary standard should be stable for a long period of time.
  2. It should rapidly react with the analyte.
  3. It should produce a sharp endpoint.
  4. It should complete the reaction by the simple chemical equation.

Indicator:

These are very weak organic acids or bases. Based on the hydrogen ion concentration present in the solution, the indicator produces different colors.  These are as follows:

1.   One-colour indicator: Example: Phenolphthalein which produce pink colour

2.   Two-colour indicator: Example: Methyl orange which produces red to yellow colour

3.   Mixed indicator: Example: Natural red and methylene blue

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