Chemical Analysis in Quality Control
for
Pharmaceutical Laboratories
Prepared by
Dr / Sherif Abo El-Azm
Part (1) : Titrations
Contents
1- Introduction
2- Titration equipment diagram
3- Volumetric Solution (VS) & Standardization (Factor)
4- Types of titration (Reaction Type)
5- Procedural (Applies to All Titration Reactions)
6- Non-aqueous titrations
Before We Start
What is titration ?
Titration (Titrimetric)
is a quantitative technique where a solution of known
composition containing a reagent—the titrant—is
quantitatively added to a defined quantity of a sample
solution that contains an unknown amount of the analyte.
Titration
The known reaction between titrant and analyte proceeds
stoichiometrically until, ideally, the volume of titrant
added equivalent to the amount of analyte in the
sample.
The difference between qualitative & quantitative analysis
in chemistry (Analysis Methods)
A. Qualitative Analysis: detects whether or not certain chemical
components are present in a sample.
B. Quantitative Analysis: determines the amount of various chemical
components present in a sample.
Titrant
The solution of known concentration and Specific Factor
Analyte
The solution of unknown concentration but known of specific
volume or Weight.
Equivalence Point
The point when volume of titrant is equivalent to the
amount of analyte.
Endpoint
The point at complete of reaction by change the
color of indicator.
Indicators
- a substances that change of different colors depending on
conditions in the surrounding medium .
- May be ( Reagent or Sensor)
- every indicator has a color in titrant change in analyte
Blank Corrections
procedure is repeated in every detail as the test
except the Analyt
Automated
Titration
Automated
Titration
Titration equipment diagram
Volumetric Solution (VS) & Standardization of Titrant
Volumetric solutions: solutions of reagents of known concentrations
intended primarily for use in quantitative determinations.
Molar solutions : solutions that contain one gram-molecule weight of the
compound (solute) in 1 L of (solvent).
Example : Na2CO3=[ (23*2)+12+(16*3)]= 106 g/mol
Normal solutions : solutions that contain one gram-equivalent weight of the
compound in 1 L .
Example : Na2CO3=[ (23*2)+12+(16*3)]/2= 53 g/mol
Volumetric Solution (VS) & Standardization of Titrant
Volumetric Solution (VS) & Standardization of Titrant
Standardization
Nominal Concentration
Factor
Purity of Reagent
Stability of concentration
Volumetric Solution (VS) & Standardization of Titrant
Factor
Volumetric Solution (VS) & Standardization of Titrant
Determined on Primary standard
Validated method (official as USP)
Standardization
Limit ± 10% of Nominal concentration
RSD of 3 Tests (NMT 0.2%)
Volumetric Solution (VS) & Standardization of Titrant
React with the titrant in a
known ratio
Primary Standard Be available in high purity,
very stable, and non-
Recommended hygroscopic
Have a high molecular weight
Types of titration (Reaction Type)
[Link] base titration
[Link] titration
[Link] titration
[Link] titration
Procedural (Applies to All Titration Reactions)
Indirect
(substitution)
Inverse Titration Direct
Residual
(back titration)
Procedural (Applies to All Titration Reactions)
Ask : How to choose the procedural/type of Reaction ?
Answer
by three conditioning
- known of stoichiometric ratio between titrant and analyt
- State of reaction (Rapid or Slow)
- Known type of titration ( direct,…..ect)
[Link] base titration
Acids and bases are most simply defined as substances when dissolved in
water give a hydrogen ions (H+) and hydroxide ions (OH−).
Note : Acid–base reactions usually occur very rapidly and
are thus predestined for direct titrations.
For Example : Assay of Citric Acid Anhydrous
[Link] base titration
Assay of Anhydrous Citric Acid
[Link] base titration
Assay of Anhydrous Citric Acid
[Link] base titration
Assay of Anhydrous Citric Acid
[Link] base titration
Assay of Anhydrous Citric Acid
2. Precipitation titration
- the reaction between titrant and the analyte leads to the formation of an
insoluble compound.
- A major difficulty for this type of titration is how to reliably identify the
endpoint, because of turbidity due to formation of very fine precipitate
particles, the co-precipitation of interfering species, or other contributing
factors.
- Due to this Recommended of determining the endpoint Potentiometrically
- For Example : Assay of Sodium Chloride Injection by
using of 0.1 N silver nitrate VS & Eosin Y TS as indicator
2. Precipitation titration
2. Precipitation titration
yellow color with sodium chloride turn to pink at [Link]
2. Precipitation titration
3. Complexometric titration
- In Complexometric titration the titrant generally forms a
complex with the analyte (usually a metal ion).
- Metal ion as Ca2+ , Mg2+
- Chelating agent as EDTA.2Na (Disodium Edetate)
- Chelating agent Helper ingredients that react with metal
ions and help to keep the formula stable.
- Formation of complexes between Metal ion and chelating
agent
3. Complexometric titration
3. Complexometric titration
Indicator–analyte-complex
less stable than
Chelating -analyte-Complex
3. Complexometric titration
- For Example : Assay of Calcium Carbonate
3. Complexometric titration
- Indicators with Specific Metal Ions
[Link] titration
• Redox titration : a reaction between titrant & analyte is an
oxidation-reduction reaction
Oxidation-reduction reaction between
Reducing Oxidizing
Agent Agent
[Link] titration
Types of indicators used in oxidation-reduction reaction
Self External Internal
Indicators Indicators Indicators
[Link] titration
[Link] titration
[Link] titration
Non-aqueous titrations
• A type of titration in which the analyte substance is dissolved in a solvent
which does not contain water.
• This procedure is a very important one in pharmacopoeia assays.
• Non-aqueous titrations are primarily carried out when:
1. The substance is not soluble in water, e.g., fats and oils
2. Single components of mixtures of acids or bases have to be determined separately
by titration
3. Suitable solvent systems should :Dissolve the sample and not react with analyte
Non-aqueous titrations
Assay of Cocaine
Non-aqueous titrations
Assay of Potassium Citrate
Assay of Dexpanthenol
Non-Non-aqueous titrations
Residual titration (back titration)
Acid-base titrations
Reference
1. USP 〈541〉 Titrimetry
2. USP (volumetric solution) General Monograph