Quantitative Analysis Basics

• Pharm. Anal. Chem. II PC 203 focuses on acid-base titrations and is covered in Lecture 1.

Course Aim

• Quantitative analysis aims to determine a sample's quantity and purity.
• Students gain a fundamental understanding of acid-base, precipitimetry, and complexometric titrations.
• The course explains the application of these titrations in drug substance analysis using different methods.
• Students learn to select suitable analysis methods, check titrimetric reaction feasibility, choose indicators, derive titration curves, and interpret results.

Acid-Base Titration Contents

• Introduction to acid-base titrations
• Acid-base theories: Definition and limitations
• Law of mass action & acid-base equilibrium in water
• pH of acid, base, and salt solutions
• Definition, types, and importance of buffer solutions in pharmacy
• Neutralization indicators: color, turbidity, & fluorescence
• Definition, types, and importance of neutralization titration curves
• Applications of acid-base titration in aqueous medium
• Acid-base titrations in non-aqueous medium

Introduction to Quantitative Analysis

• The aim is to determine the quantity of the substance under analysis

Classification of Quantitative Analysis

• Macro-analysis: > 100 mg sample
• Semi-micro analysis: 10 – 100 mg sample
• Micro-analysis: < 1.0 mg sample

Classification According to Method of Analysis

• Gravimetric analysis: Analysis by weight.
• Volumetric analysis, where a standard solution (titrant) reacts with a sample.
• Instrumental analysis: Depends on measuring physical properties quantitatively related to the concentration of sample, mainly based on optical and electrical phenomena

Volumetric Analysis Details

• Volumetric analysis or titrimetry involves adding a reagent (titrant) to a solution containing another reagent (titrand), allowing them to react.
• Titrant: A solution of known concentration added to another solution.
• Titrand or analyte: A solution whose concentration has to be determined.

Volumetric Analysis Types

• Divided into four categories based on the type of reaction:
  • Acid-base titrations: Involve the reaction of an acidic or basic titrant with a titrand that is a base or an acid, forming slightly ionized water
    • H+ + OH- ⇋ H₂O
  • Complexometric titrations: Based on metal-ligand complexation
    • Example: Ag+ + 2CN- → [Ag(CN)2]- & Ca 2+ + H₂ Y2- (EDTA anion) → 2 H+ + Ca2 Y2
  • Precipitation titrations: Involve the formation of a precipitate between the titrand and titrant
    • Example: Ag+ + Cl- → AgCl (white ppt)
  • Redox titrations: Use an oxidizing or reducing agent as the titrant
    • Example: Ce4+ + Fe2+ → Ce3+ + Fe3+

Titrimetric Reaction Requirements

• Simple reaction expressed by a chemical equation
• No side reaction
• Very rapid reaction
• Availability of a suitable standard solution
• Ease of end point detection

Titrimetry Error Sources

• Loss of sample
• Contaminations
• Improper mixing
• Weighing errors
• Dilution errors
• Reading errors
• Use of wrong indicators
• Personal errors

Key Analysis Terms

• Accuracy: Agreement between a measured value and the accepted true value.
• Precision: The degree of agreement between replicate measurements of the same quantity.
• Analyte: The constituent of a sample to be studied by quantitative measurements or identified quantitatively.
• Standard solutions (titrants): Solutions of exactly known concentration, important in volumetric analysis.
• Primary standard: A highly purified substance of known concentration, used as a reference material.
• The Equivalence point: Theoretical completion of reaction (end of titration).
• End Point: The practical completion of the reaction.
• Titration error: The difference between the equivalence point and the end point.

Standard Solutions

• Standard solutions are of exact and known concentration.

Types of Standard Solutions

• Molar Standard Solutions (M)
• Normal Standard Solutions (N)

Methods for Expressing Solution Concentration

• Molar Standard Solutions (M): Solutions containing gram Molecular Weight in one liter.
• Normal Standard Solutions (N): Solutions containing gram Equivalent Weight in one liter.

Equivalent Weight Calculations

• Equivalent Weight of Acids:
• Eq. Wt = Molecular weight / Number of replaceable H+
• Examples:
  • Eq.Wt of HCI = Mwt of HCI / 1
  • Eq.Wt of H2SO4 = Mwt of H2SO4 / 2
• Equivalent Weight of Bases: Eq.wt = Molecular weight / Number of replaceable OH-
• Examples: Eq.wt of NaOH = M.wt / 1, Eq.wt of Ba(OH)2 = M.wt / 2
• Equivalent Weight of Salts: Eq.wt = Molecular weight / Number of ions X valency Examples:
• Eq.wt of Na2CO3 = M.wt / 1 X 2
• Eq.wt of Na3PO4 = M.wt/ 1 x 3
• Solutions with the same normalities react together in equal volumes.
• Example: 10 ml of 0.1N HCI reacts with 10 ml of 0.1N NaOH, and 8ml of 0.1N Na2CO3 reacts with 8ml of 0.1N HСІ

Other Solutions Concentration Types

• % W/V: gm/100 ml
• % W/W: gm/100 gm
• % V/V: ml / 100 ml
• Ppm: mg/Kg (1mg/1000000 mg, i.e., 1 part/ million)

Titer Definition

• Weight of sample (analyte or titrand) chemically equivalent to 1 ml of titrant, expressed in milligrams.
• Example: If 1 ml of titrant 0.1N hydrochloric acid solution exactly neutralizes 4 mg of sample sodium hydroxide, the titer is 4 mg/ml.

Primary Standards

• Substances of definite known composition and high purity.
• Easily obtained in a very pure form.
• Easily tested for impurities.
• Stable, non-hygroscopic, and non-volatile.
• Readily soluble.
• Should have a high eq. wt to decrease the weighing errors.
• React stoichiometrically with other substances.
• Examples: Potassium Acid phthalate, anhydrous Na2CO3, and benzoic acid.

Secondary Standards

-These do not fulfill all primary standard requirements

• Examples: NaOH, HCl, Hydrated oxalic acid, and Hydrated borax.
• Require standardization against a primary standard
• Example: Lab 1: standardization of HCl (secondary standard) with standard sodium carbonate (primary standard

Standard Solutions Preparation

• Direct Method: Accurately weighed solute dissolved and made up to the required volume
  • Solute must be of primary standard quality
• Indirect Method: Solute not of primary standard quality, approximate concentration standardized against a primary standard

Acid-Base Titrations in Aqueous Media

• Many drugs are acidic, basic, or amphoteric when dissolved in water or other solvents.
• Examples:
  • Acids: Aspirin, sulphonamides, morphine, and penicillins.
  • Bases: Alkaloids (atropine, codeine, epinephrine).

Dissociation Theory

• When an electrolyte dissolves in water, it dissociates into cations and anions.
• Molecules ⇋ Cations + Anions
• Degree of dissociation (α) = (number of solute molecule dissociated) / (Total number of solute molecule before dissociation)
• Reversible equilibrium exists between undissociated molecules and ions
• When dissociation is complete, α will be unity or nearly so (strong electrolyte)
• When dissociation is weak, α is far from unity (weak electrolyte)
• Example: HCl → H+ + Cl- (strong electrolyte)
• CH3COOH ⇋ H++ CH3COO- (weak electrolyte)

Acid-Base Theories

• Arrhenius Theory: Acid ionizes into H+, bases give OH
• Acid: any substance that ionizes to give H+
• Base: any substance that ionizes to give OH-
• Did not discuss the solvent's role in ionization
• Brønsted-Lowry Theory: Acid donates H+, base accepts H+
• Acid: substance that donates H+
• Base: substance that accepts H+
• The solvent is involved in the reaction as an acid or a base
• Water acts as an acid or a base
• Lewis Theory: Base contains an atom with an unshared pair of electrons to share, while an acid accepts to share this electronic pair
• An acid: Any substance that accepts electrons
• A base: Any substance that donates electrons
• Compounds without OH can be alkaline Compunds withouth H+ are acids

Law of Mass Action

• Velocity (or rate) of a chemical reaction that is proportional to the product of the active masses of the reacting substances
• aA + bB CC + dD
• where a,b,c,and d are the coeficient of the reacting substances.
• At equilibrium Vf=Vb
• Kf [A].[B] = Kb [C].[D]
• Kf [A].[B] = Kb [C].[D]
• Kf / Kb = Keq "Equilibrium Constant"
• Keq = C].[D] / [A].[B]

Explore quantitative analysis principles, including titrations and gravimetric methods. Learn about titrants, titrands, and acid-base titrations in aqueous solutions. Understand the goal of quantitative analysis and develop skills in analytical methods.