Pharmaceutical Analytical Chemistry II (PC 203)

Lecture 1
Dr. Hatem Mokhtar
Lecturer of Analytical Chemistry
Faculty of Pharmacy

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Pharmaceutical Analytical Chemistry II (PC203)

Course overview

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DENTISTRY/ second year/ SU/ lect 6 www.su.edu.eg
Course Overview
• Introduction to quantitative analysis → titrimetric analysis
• Neutralization reactions I: Acid-Base titration in Aqueous medium
• Neutralization reactions II: Acid-Base titration in Non-Aqueous
medium
• Complexation reactions and complexometric titrations
• Precipitation reactions and precipitimetric titrations

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 Lecture 1
Quantitative analysis
Titrimetric Analysis

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DENTISTRY/ second year/ SU/ lect 6 www.su.edu.eg
Quantitative Analysis
• Objectives:
• To Know what is meant by quantitative analysis.
• To differentiate between different types of quantitative analysis.
• To know the requirement of quantitative analysis.

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Quantitative Analysis Introduction For information
only
• Introduction:
• When a completely unknown sample is presented to an analyst, the first
requirement is usually to ascertain what substances are present in it
(Identification).
• This fundamental problem may sometimes be encountered in the
modified form of deciding what impurities are present in a given sample
(impurity identification and profiling), or perhaps of confirming that
certain specified impurities are absent (Confirmation of detection).
• The solution of such problems lies within the province of qualitative
analysis and is outside the scope of the present course.
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Quantitative Analysis Introduction
• Introduction (Cont.):

• Having ascertained the nature of the constituents of a given sample

( by identification of confirmation of detection); the analyst is then

requested to determine how much of each component(s), is present.

• → Quantitative Analysis
For information
only

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Types of Analysis and factors affecting method selection
• Important factors that must be taken into account when selecting an
appropriate method of analysis include:
• (A) sample amount: how much sample is provided for analysis
• (B) Constituent concentration in Sample: The % of the target analyte
in your sample
• (C) The process of measurement : how would you analyze the
sample

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Types of Analysis: according to Sample amount
1. Macro, the analysis of quantities of 10-1g (≥0.1 g) or more

2. Meso (semimicro), for quantities ranging from 10-2g (≥ 0.01g) to less than 10-1 g
(<0.1g)

3. Micro, for quantities in the range from 10-3g (≥0.001g) to less than 10 -2 g (<0.01g)

4. Submicro, for samples in the range from 10-4g (≥ 0.0001g) to less than 10 -3 g(<0.001g)

5. Ultramicro, for quantities below 10 -4 g (<0.0001g)

• e.g. Macro-analysis, micro-analysis,…

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Types of Analysis: according to Sample amount

Sample amount Analysis type

• 10g • Macro
• 0.1g • Macro
• 0.08g • Semimicro or meso
• 1.2x10-3g • Micro
• 0.0002g • Submicro
• 10-3g • Micro
• 1.5x10-5g • Ultramicro

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Types of Analysis: according to Constituent Concentration

• A major constituent is one accounting from ≥1% to 100% of the

sample under investigation

• A minor constituent is one present in the range from ≥ 0.01% to less

than1%

• A trace constituent is one present at <0.01%

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Types of Analysis: according to Constituent Concentration

Constituent concentration Analysis / constituent type

• 10% • Major

• 1% • major

• 0.5% • minor

• 0.1% • minor

• 0.01% • minor

• 0.2g constituent dissolved in 10L solvent • (0.2/10000)x100%= 0.002% trace

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Types of Analysis: Process of Measurement
1. Titrimetric or Volumetric analysis
– To be detailed in this course
2. Gravimetric analysis:
– Weighing of the final product of reaction after its isolation. The isolated product
must be pure and stable form of definite chemical structure.
3. Instrumental Analysis:
– Physico-chemical methods which depend mainly on optical and electrical
properties.
– By measuring these properties which are quantitatively related to the analysed
constituent, we can find its concentration. e.g spectrophometric, potentiometric
and conductometric methods of analysis.
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Titrimetric or Volumetric Analysis
• Principle of Titremtry
• Assume the analyte A (e.g. an acid)is present in unknown quantity in a
solution
• If we know that the substance B (for this example a base) reacts
completely with the analyte A:
A+B→AB
• The we can determine A amount in the sample by reacting it with the
substance B (added portion-wise) till no amount of A remains.
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Titrimetric or Volumetric Analysis
• Principle of Titremtry (cont.)
A+B→AB
• According to the equation of the reaction, we can measure the unknown
amount of A by knowing how much compound B is consumed to complete
the reaction(the end point).
• To add the compound B to the reaction we prepare it in a solution of
accurately known concentration (Titrant or standard solution).
• By knowing the volume consumed (end point) from the titrant / standard
solution; the amount of unknown substance A could be calculated.

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Titrimetric or Volumetric Analysis
• The term 'titrimetric analysis' refers to:
• A quantitative chemical analysis.
• It is carried out by determining the volume of a solution of accurately
known concentration which is required to react quantitatively with a
measured volume of a solution of the substance to be determined.
• The solution of accurately known strength is called the standard solution.
• The term 'volumetric analysis' was formerly used for this form of
quantitative determination but it has now been replaced by titrimetric
analysis.

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Titration
• A titration is a procedure for determining the amount of substance A by
adding a carefully measured volume of a solution with an accurately
known concentration of B until the reaction of A and B is just complete.

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Titration (Revision)

Burette

Standard solution
(titrant)

Sample solution containing

substance to be determined
(Analyte)

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Types of Titrimetric Analysis According to Reactions
• A- Ionic combination reactions
• They are reactions that proceed to completion due to formation of
slightly ionized or slightly soluble products. they include:
– Acid-Base Neutralization reactions
– Complex formation reactions
– Precipitation reactions
• B-Electron transfer reactions
– Oxidation reduction reactions

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Types of Titrimetric Analysis According to Reactions
Acid-Base Neutralization reactions (Acidimetry or Alkalimetry):
• The reactions involve the combination of proton cations and hydroxide anions to form water.
𝑯𝑪𝒍(𝒕𝒊𝒕𝒓𝒂𝒏𝒕) + 𝑵𝒂𝑶𝑯 (𝑨𝒏𝒂𝒍𝒚𝒕𝒆) → 𝑵𝒂𝑪𝒍 + 𝑯𝟐 𝑶
• They include:
• Acidimetry: The titration using an acidic titrant for a determination of a basic sample.
• Basic sample could be:
– free bases
– Salts of weak acids with strong bases

• Alkalimetry: The titration using an basic titrant for a determination of a acidic sample.
• Acidic sample could be:
– free Acids
– Salts of weak Bases with strong Acids

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Types of Titrimetric Analysis According to Reactions
• B- Complex formation reactions
• These depend upon the combination of ions (other than hydrogen or
hydroxide ions) to form a soluble, slightly dissociated ion or compound
(to be discussed later).

𝑪𝒂𝟐+ (𝑨𝒏𝒂𝒍𝒚𝒕𝒆) + 𝒚𝟒− 𝑫𝒊𝒔𝒐𝒅𝒊𝒖𝒎 𝒆𝒅𝒆𝒕𝒂𝒕𝒆 𝒕𝒊𝒕𝒓𝒂𝒏𝒕 → 𝑪𝒂 𝒚𝟐− (Calcium edetate complex)

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Types of Titrimetric Analysis According to Reactions
• C-Precipitation reactions
• These depend on the combination of ions to form a simple
precipitate as in the titration of silver ion with a solution of chloride.
No change in oxidation state occurs(to be discussed later).

𝑨𝒈+ (𝒕𝒊𝒕𝒓𝒂𝒏𝒕) + 𝑪𝒍− (𝒂𝒏𝒂𝒍𝒚𝒕𝒆) → 𝑨𝒈𝑪𝒍 ↓(weakly dissociated)

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Types of Titrimetric Analysis According to Reactions
• D-Oxidation-reduction reactions
• A type of electron transfer reactions. All reactions involving change of
oxidation number or transfer of electrons among the reacting
substances. The standard solutions are either oxidizing or reducing
agents (to be discussed later).

𝑪𝒆𝟒+ (𝒕𝒊𝒕𝒓𝒂𝒏𝒕, 𝒔𝒕𝒓𝒐𝒏𝒈 𝒐𝒙𝒊𝒅𝒂𝒏𝒕) + 𝑭𝒆𝟐+ (𝑨𝒏𝒂𝒍𝒚𝒕𝒆, 𝒔𝒕𝒓𝒐𝒏𝒈 𝒓𝒆𝒅𝒖𝒄𝒕𝒂𝒏𝒕) → 𝑪𝒆𝟑+ + 𝑭𝒆𝟑+

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Titrimetric Analysis
What are the Requirements for titrimetric reactions???
1. Must be simple reaction expressed by single chemical equation.
2. Single reaction must occur between the desired constituent and the
titrant only (i.e. The titrant is selective for the constituent).
3. Rapid reaction between the titrant and the analyte
4. Suitable standard solution must available in solution form as titrant.
5. End point should be easily detected by physical or chemical change
in the solution.

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Titrimetric Analysis
• To perform titrimetric analysis for any sample you will need the
folllowing:
• 1- Calibrated bulb pipettes for taking sample
• 2- Calibrated burettes for standard solution (titrant)
• 3- Standard solution (Titrant): a solution of exactly known
concentration of a substance that reacts with the sample compound
to be determined.

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Standard Solutions
• Standard solution concentrations may be expressed as:
• Empirical Standard Solution )‫(تجريبي‬
• Molar Standard Solution
• Normal Standard Solution

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Standard Solutions expression
• Empirical Standard Solution )‫(تجريبي‬

These are standard solutions that we cannot express their concentrations relative to the standard
material they are made from.

Instead we express their concentration relative to the amount of analyte they are able to react with.

The empirical standard concentration is expressed as follows: in such concentration that 1 ml of that
standard solution is equivalent to certain amount of the target analyte. This amount is calculated by an
initial experiment that measure the amount of the analyte that reacts with each ml of titrant.

They are used in the determination of only one substance which they are made to analyze.

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Standard Solutions expression
• Empirical Standard Solution )‫(تجريبي‬

Example 1:

Karl-Fisher reagent: it is a mixture of compounds that is used only for determination of water content.

Its concentration could be expressed as: each 1ml of karl fisher reagent is equivalent to x mg of water.

Example2:

Dichlorophenol-indophenol standard solution is used only for determination of ascorbic acid.

Its concentration could be expressed as : Each 1ml of the titrant is equivalent to x mg of the analyte

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Standard Solutions expression
• Molar Standard Solution
- One Molar standard Solution: a Standard Solution that contain one
gram molecular weight (i.e. 1 Mole) of the substance in one liter of
solution.
Molarity: Number of Moles/ liter

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Standard Solutions expression
• Molar Standard Solution
• How to calculate amount of standard material needed for preparation of
a standard solution of certain molarity at certain volume:
(Required molarity) x (Molecular weight of the standard material) x Required volume per Liter

• For example:
• Prepare 0.5 L of 0.01 M KOH (Mwt=56.1)
• KOH amount= 0.01 (required Molarity) x (56.1 Mwt) x (0.5 Vol)= 0.28 g to
be dissolved into 0.5 L.

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 THANK YOU
For any questions feel free
to contact me by mail
Hatem.mokhtar@su.edu.eg

Dr Hatem Ibrahim Mokhtar

Lecturer of Analytical Chemistry (FOP-SCU)