The document outlines techniques in volumetric analysis, focusing on methods such as titration for determining the concentration of unknown solutions. It discusses key concepts like standard and unknown solutions, the titration process, types of titrations, and various methods for detecting endpoints. Additionally, it highlights the importance of accuracy, precision, and reliability in pharmaceutical analysis.

1. ANALYSIS
MS. KAD DHANASHREE R.
ASSISTANT PROF. P’CAL CHEMISTRY
PES MODERN COLLEGE OF PHARMACY (FOR
LADIES), MOSHI,PUNE

2. • Volumetric analysis deals with the measurement of
volume of solutions involved in the chemical reactions
which ultimately lead to the determination of the
amount of the constituents of the substance.
• A chemical test is a qualitative or quantitative
procedure designed to prove the existence of, or to
quantify, a chemical compound or chemical group
with the aid of a specific reagent.
• A presumptive test is specifically used in
medical and forensic science.

3. Pharmaceutical analysis is the quantitative
measurement of the active ingredient and related
compounds in the pharmaceutical product
These determinations require the highest
accuracy, precision, and reliability because of the
intended use of the data as in:
1.Manufacturing control (identify drug in
formulation),

4. 2.Stability evaluation (determine the impurity
and degradation products in the stability study),
and shelf-life prediction.
3.Determination of drugs and their metabolites in
biological samples, generally plasma or urine, is
important in elucidation of drug metabolism
pathways as well as comparing bioavailability
of different formulas.

5. There are several methods used in chemical
analysis starting from simple manual
method to complicated and sophisticated
ones of these are: titration,
spectrophotometric ,HPLC with multi
detectors ,……….etc

6. • The amount of the substance present in the definite
quantity of the solution is called concentration of
thesolutions.
• There are many ways of expressing the
concentration of the solution. The concentration of
the solution can be expressed in any of the
following ways.
• The amount of the solute in gram present in one litre
of the solution is known as gram per litre of the
solution.
Eg. If 5 gram of NaOH is dissolved in 500 ml of the
solution thenits strength is 10 g/l.

7. • The number of gram equivalent of solute present in a litre of
the solution is known as normality of the solution.
• Normal solution(1 N)Seminormal solution (N/2)
• Decinormal solution (N/10) Centinormal solution (N/100)
Pentanormal solution (5N) Decanormal solution (10N)
• The number of the moles of solute present in a litre of
the solutions is known as molarity of the solutions

8. • Percentage strength means number of parts of solute in 100
parts of solution which is expressed in three different
ways:
a. % in weight by weight (w/W): it may be defined asthe amount
of solute in grampresent in 100gramof the solution.
Simply,
%byw/W =(wt of solute in gm/wt of the solution in gm)×100%
b.% in weight by volume (w/V): it may be defined asthe amount
of solute in grampresentin 100ml of the solution.
Simlpy,
%byw/V =(wt of solute in gm/volumeof the solution in ml)
×100%c.%involumebyvolume(v/V):it maybedefined asthe volume
of solute in ml presentin 100ml of thesolution.
Simply,
%byv/V =(volume of solute in ml/volume of the solution in
ml) × 100%

9. Thenumber of the molesof solute present in one kgof solvent is known
asmolality of thesolution.
Molality =(no.of molesof solute )/ (wt of solventin Kg)
• Unknown solution: The solution whose strength is not
known i.e. the solution whose strength is to be
determined during the titration is known as unknown
solution.
• Standard solution: The solution whose strength is
known isknownas standard solution.

10. Titration:
Theprocessin which the concentration of unknown solution is determined with
the help of standardsolution byusingthe indicator is calledtitration.
Titrant
Thesolution of known concentration which isusuallytakenin aburette iscalledtitrant.
Titrand:
The solution of unknown concentration which is being titrated and usually taken in a
conicalflaskiscalledtitrand.
• Endpoint:
• Thepoint in atitration at which reaction between two solution is
just completed and at which indicator canshowsharp colour
changeis called endpoint.

11. Equivalencepointortheoreticalpoint:
•The stage during the titration at which exactly equivalent amount of
titrant isaddedto titrand isknown asequivalencepoint.
• In theoretical concept, when equivalent amount of titrant is added to
the titrand, the indicator shouldchangethe colour and
indicate the end point. But in actual practice, the indicator doesn’t
change its colour at equivalence point. This is because the indicator
changesits colour either in acidicoralkaline medium. Thereforein
practice asmalldifference occursbetween equivalencepoint andend
point. Thisdifference in titration isknown astitrationerror.

12. Primarystandardsubstance:
• The substance whose standard solution can be prepared directly by
dissolving the known weight of the substance in fixed volume the
solutionisknown as
primary standard substance. E.g. anhydrous sodium carbonate, oxalic
acid, silver nitrate etc.The solution of primary standard substance is
known asprimary standardsolution.
Requirementsforasubstancetobeprimary standard
• Itmust beavailablein pure form andshouldbenon toxic.
• It should not be hygroscopic( ability to absorb moisture) or
deliquescent(turns to solution).
• It should have high molecular weight or equivalent weight so as to
minimise the weighingerror duringweights.
• It shouldbereadily dissolveinwater.
• It should be stable. In other words, the composition of substance
should not changein solid or in solution statefor longtime.

13. Secondarystandardsubstance:
 Thesubstancewhosesolution canbestandardise or strength can
be determined bythe help of primary standard solution isknown
as secondarystandard substanceandthe solution isknown as
secondary standard solution. Eg.NaOH,HCl,KMnO4, FeSO4.
Normalityfactor:
It isdefined asthe ratio of actual weight of the substance
taken to the theoretical weight of the substancetobe taken
and usually denoted by “f”.

14. Applications
1. Provide standard pharmacopeial methods
for the assay of unformulated drugs and
excipents and some formulated drugs e.g.
those lack strong chromophore
2. Used for standardization of raw materials and
intermediates used in drug synthesis.
3. Certain specialist titration such as Karl
Fischer

15. Advantages
1. Capable of higher degree of precision and
accuracy.
2. The method are generally robust
3. Analysis can be automated
4. Cheap to do and not require specialized
apparatus

16. Limitations
1. Non selective
2. Time consuming if not automated and
require greater level of operator skill
3. Require large amount of sample
4. Reaction of standard solution should be rapid
and complete 1]

17. Titration curves
A titration curve is a curve in the plane whose x-
coordinate is the volume of titrant added since
the beginning of the titration, and whose y-
coordinate is the concentration of the analyte at
the corresponding stage of the titration (in an
acid-base titration, the y-coordinate is usually
the pH of the solution).

18. Types of titrations:
There are many types of titrations with
different procedures and goals. The most
common types of quantitative titration are acid
base titrations and redox titrations.

19. 1. Acid base titrations
Acid-base titrations depend on the neutralization
between an acid and a base when mixed in solution.
In addition to the sample, an appropriate indicator
is added to the titration chamber, reflecting the pH
range of the equivalence point. The acid-base
indicator indicates the endpoint of the titration by
changing color.

20. Indicator Color on acidic side Range of pH color change Color on basic side
Methyl Violet Yellow 0.0–1.6 Violet
Bromophenol Blue Yellow 3.0–4.6 Blue
Methyl Orange Red 3.1–4.4 Yellow
Methyl Red Red 4.4–6.3 Yellow
Litmus Red 5.0–8.0 Blue
Bromothymol Blue Yellow 6.0–7.6 Blue
Phenolphthalein Colorless 8.3–10.0 Pink
Alizarin Yellow Yellow 10.1–12.0 Red

21. Redox titrations are based on a reduction-oxidation
reaction between an oxidizing agent and a reducing
agent. A potentiometer or a redox indicator is usually
used to determine the endpoint of the titration, as
when one of the constituents is the oxidizing agent
potassium dichromate, the color change of the
solution from orange to green is not exact, therefore
an indicator such as sodium diphenylamine is used.

22. Some redox titrations do not require an
indicator, due to the intense color of the
constituents. For example, in permanganometry
a slight faint persisting pink color signals the
endpoint of the titration because of the color of
the excess oxidizing agent potassium
permanganate.

23. Complexometric titrations rely on the formation
of a complex between the analyte and the titrant.
In general, they require specialized indicators
that form weak complexes with the analyte.
Common examples are Eriochrome Black T for
the titration of calcium and magnesium ions, and
the chelating agent EDTA used to titrate metal
ions in solution.

24. • Back titration is a titration done in reverse;
instead of titrating the original sample, a known
excess of standard reagent is added to the solution,
and the excess is titrated. A back titration is useful
if the endpoint of the reverse titration is easier to
identify than the endpoint of the normal titration,
as with precipitation reactions.

25. There are different methods to determine the
endpoint include:
1. Indicator: A substance that changes color in
response to a chemical change. An acid-base
indicator (e.g., phenolphthalein) changes color
depending on the pH. Redox indicators are also
used. A drop of indicator solution is added to
the titration at the beginning; the endpoint has
been reached when the color changes.

26. 2. Potentiometer: An instrument that measures
the electrode potential of the solution. These are
used for redox titrations; the potential of the
working electrode will suddenly change as the
endpoint is reached.
The pH meter is a potentiometer with an
electrode whose potential depends on the
amount of H+ ion present in the solution. (This
is an example of an ion-selective electrode.)

27. 3. Conductivity: A measurement of ions in a
solution. Ion concentration can change
significantly in a titration, which changes the
conductivity. (For instance, during an acid-base
titration, the H+ and OH- ions react to form
neutral H2O.) As total conductance depends on
all ions present in the solution and not all ions
contribute equally (due to mobility and ionic
strength).

28. 4.Color change: In some reactions, the solution
changes color without any added indicator. This is
often seen in redox titrations when the different
oxidation states of the product and reactant produce
different colors.
5.Spectroscopy: Used to measure the absorption of
light by the solution during titration if the spectrum of
the reactant, titrant or product is known. The
concentration of the material can be determined by
Beer's Law.

29. 6. Precipitation: If a reaction produces a solid, a
precipitate will form during the titration. A
classic example is the reaction between Ag+ and
Cl- to form the insoluble salt AgCl. Cloudy
precipitates usually make it difficult to
determine the endpoint precisely. To
compensate, precipitation titrations often have to
be done as "back" titrations .

30. 7. Amperometry: Measures the current
produced by the titration reaction as a result of
the oxidation or reduction of the analyte. The
endpoint is detected as a change in the current.
This method is most useful when the excess
titrant can be reduced, as in the titration of
halides withAg+.

31. 8. Isothermal titration calorimeter:
An instrument that measures the heat produced
or consumed by the reaction to determine the
endpoint. Used in biochemical titrations, such
as the determination of how substrates bind to
enzymes.