MODULE 4:

Principles of Volumetric Analysis

Introduction to Volumetric Analysis

Employing Neutralization Reactions
Titrimetric Methods of Analysis

• ​Analytical methods in which a volume of a

solution of known concentration consumed
during an analysis is taken as a measure of the
amount of active constituent in a sample being
analyzed.
E.g. HCl assayed by a known concentration of
NaOH
 HCl + NaOH ​ ​NaCl + H​2​O

• ​Titrants are usually added by means of burets. ​•

Titration is the act of adding and measuring the
volume of titrant used in the assay or; the
experimental way of determining equivalent
amounts of reactants have reacted together.
Key Terms
• ​Indicators are chemicals that changes in color at
or very near point at which equal amounts of
titrant and analyte have reacted.

• ​Stoichiometric Point/Equivalence Point is the

theoretical point at which equivalent amounts of
titrant and analyte have reacted.
 • ​End Point is the stage at which titration is
stopped, where a color change in the reaction
mixture is apparent due to the presence of an
indicator.

*Titration is only feasible when end point is very

close to the stoichiometric point.
Direct, Residual and Indirect Titration
• ​Direct titrimetric methods employ that the titrant
is directly added to the analyte.
• ​Residual or back titrations, though, employ that a
carefully measured volume of standard solution
known to be chemically in excess, is added first
 to the analyte. The excess being back titrated by
another standard solution.
E.g. Assay of ZnO using standard H​2​SO​4​and NaOH
solutions
Indirect titrations employ that the analyte be
treated first with an agent that converts it to an
easily measurable substance, which can be easily
titrated by a standard solution.
E.g. Iodometric Methods
Other Key Terms in Volumetric Analysis
Gram-Equivalent Weight (GEW)
• ​Weight in grams which is chemically equivalent
to 1 gram-atom of hydrogen (1.0079g)
• ​In neutralization, it is defined as the weight of a
substance in grams which contains, furnishes,
reacts with directly or indirectly or replaces 1
gram-atom or ion of hydrogen.

• ​In redox reactions, it is the weight of a reducing

agent or oxidizing agent that loses or gains
electrons. It is calculated by dividing the gram
molecular weight by the number of electrons lost
or gained.
Other Key Terms in Volumetric Analysis

Gram-Milliequivalent Weight
(GmEW/mEq) ​• ​GEW/1000, expressed as
g/mEq
• ​In titration, two substances reacting upon
reaching the end point must have the same
number of mEq or equivalents

Standard Solution
• ​Solution of known concentration (N or M)

Normality
• ​GEW/L or GmEW/mL
Other Key Terms in Volumetric Analysis
Molarity
• ​mol/L

Standardization
• ​Determination of N or M of a solution by
using a primary standard or a secondary
standard

Primary Standard
• ​Carefully weighed sample of known purity
Other Key Terms in Volumetric Analysis
Secondary Standard
• ​A solution of known concentration which can be
used to determine the concentration of another
solution.
E.g. HCl solution can be standardized using
anhydrous Na​2​CO​3 or
​ by standard NaOH
solution.

Titer
• ​Weight of a substance chemically equivalent to
1mL of a standard solution.
• ​Usually expressed in g or mg
• ​Titer values are often specified in assay
procedures in official monographs.
 Calculation of Titer Value
1.) How many mg of NaOH is equivalent to 1mL of
1N HCl solution?
NaOH + HCl ​ ​NaCl + H​2​O
40.00
Titer (g) = V x N x GmEW or mEq
1mL x 1N x 0.04g/mEq
= 0.04g ​ ​40mg NaOH is equivalent to 1mL of 1N
HCl
2.) Calculate the titer value of Ca(OH)​2​in g, against
0.1N HCl.
Ca(OH)​2 +​ 2HCl ​ ​CaCl​2 +​ H​2​O
74.08
Titer = 1mL x 0.1N x 0.03704g/mEq
= 0.003704g Ca(OH)​2​is equivalent to 1mL of 0.1NHCl
Calculation of Titer Value
3.) How many mg of H​2​O​2​is chemically
equivalent to 1mL of 0.1N KMnO​4​?
5H​2​O​2 +​ 2KMnO​4 +​ 3H​2​SO​4 ​ ​5O​2​↑ + ​2MnSO​4
+ K​2​SO​4 +​ 8H​2​O
MW H​2​O​2 =​ 34
Titer = 1mL x 0.1N x 0.017g/mEq
= 0.0017g ​ ​1.7mg of H​2​O​2​is equivalent to
1mL of 0.1N KMnO​4

4.) Calculate the titer value of 0.1N H​2​SO​4​.

Titer = 1mL x 0.1N x 0.04903g/mEq =
0.004903g or 4.903mg H​2​SO​4 is​ present in ​1mL
of 0.1N H​2​SO​4​solution
Volumetric Apparatus
• ​Those that are made to deliver a definite volume
of liquid.
Burets and Pipets
• ​Those that are made to contain a definite volume
of liquid.
Volumetric Flasks and Graduated Cylinders

• ​Temperature specified by USP/NF is 25​o​C while

the National Bureau of Standards has adopted
20​o​C.
• ​Hence, equipments calibrated at specified temp
should be followed and be the same for a series
 of measurements.
• ​Milliliter has been adopted as the official unit of
capacity for volumetric analysis.
Burets
• ​Precisely manufactured glass tube with graduations
enabling measurement of volumes of liquids delivered
through the stopcock at the bottom.

• ​Graduated glass tubes of uniform bore throughout its

whole length, used in the measurement of variable
quantities of liquids.

• ​Closed at the bottom by a glass or Teflon stopcock to

control the outflow of liquid.
 • ​Should be tested for leakage before use
Burets

• ​Glass stopcocks may require lubricants to seal off

leakage and permit ease of operation.

• ​Teflon stopcocks may require the adjustment of its

knurled nut for proper operation.

• ​The outlet tip of either type should deliver a drop with a

volume considerably less than that of the finest
graduation of the buret.
Reading Burets
• ​The surface of liquids in narrow tubes is always curved,
because of capillarity and adhesive forces.
• ​This curve is always concave when the liquid wets the
tube and convex when not.
• ​Readings should always be done below meniscus, except
for highly colored liquids.
• ​The eye must be at the same level of the meniscus,
otherwise parallax error will be introduced.

Pipets
• ​Should be graduated to deliver at standard temp
the volume indicated.

• ​Pipets labelled TD should never be drained by

blowing while Pipets labelled B, should be
drained by blowing.

• ​Filled to about 1cm above the zero mark and any

adhering liquid at the outer surface should be
carefully wiped off and the pipet is allowed to
drain down to the zero mark.

• ​The liquid is drawn up by an aspirator or pipet

filler and never by the use of an analyst’s
 mouth.
Volumetric Flasks and Graduated
Cylinders
• ​Volumetric flasks should be graduated to
contain the indicated volume at 25​o​C when
filled to the mark.
• ​Volumetric flasks are used to make up
standard solutions to a given volume.

• ​Graduated cylinders are used in making

accurate measures of volume.
• ​Graduated cylinders should be graduated to
contain a given volume of liquid at standard
 temperature.
• ​The inside diameter should not exceed one ​
fifth
of the graduated length.
Cleaning Volumetric Apparatus
• ​New apparatus should always be cleaned prior to
use. From there on, it should be cleaned every
after each use.
Indications of a Dirty Apparatus:
• ​Adherence of droplets to the walls of the
apparatus.
• ​The liquid it contains drains non-uniformly. The
walls are not wet uniformly, leaving droplets
that ​are observable.
Best Cleaning Solutions:
• ​Warm solution of Na​2​Cr​2​O​7​in H​2​SO​4​, Na​3​PO​4
solution and synthetic detergents
• ​Hot solutions should be avoided as this may
cause a possible permanent change in the
volume of the apparatus.
Calibration of Volumetric Apparatus

• ​Available apparatus in the market is calibrated at

different temp, depending on the supplier. Hence,
the analyst should always check the calibration of the
apparatus and make corrections as necessary.

• ​Calibration is the process of measuring the actual

quantity of mass, volume, etc. that correspond to an
indicated quantity on the scale of an instrument.
• ​Burets are calibrated by withdrawing successive ​10mL
portions of distilled water and are corrected on ​the
basis of:
Calibration of Volumetric Apparatus

Burets calibrated at 20​o​C should deliver

9.9718g of water, equivalent to 10mL,
weighed at 50% humidity and 1atm.

Burets calibrated at 25​o​C should deliver

9.9604g of water, equivalent to 10mL,
weighed at 50% humidity and 1atm.
 Pipets are calibrated by obtaining the
weight of water it can deliver. Flasks are
filled to the mark and weighed.
Sources of Error in the Use of Volumetric
Apparatus
1.) Water adhering to the walls of the
apparatus
• ​Dry the apparatus or wash it with the liquid
to be used.
2.) Grease and dirt causing irregularities in
meniscus formation and liquid delivery. ​•
Wash with prescribed cleaning solutions.
 3.) Drainage or afterflow of the liquid adhering
to the vessel walls.
• ​The time of drainage after filling the
apparatus up to the mark should be the
same during calibration/re-calibration. ​4.)
Parallax error
Sources of Error in the Use of Volumetric
Apparatus
5.) Temperature variations leading to change
in volume of the apparatus
• ​Measurements should be made at temperatures
with close approximation to the temperature
during calibration/re-calibration.
6.) Air bubbles trapped beneath the liquid
surface ​• ​Displace the liquid.
7.) Heat
8.) Most salts produce temperature change when
dissolved, and further, volume change.
• ​Should never be measured unless they have
acquired the temp at which the apparatus is
calibrated.
9.) Failure to use apparatus in the right manner.
Chemical Reactions Used in
Titrimetry
• ​Chemical Reactions that are used extensively in
the analysis of drugs and dosage forms official in
the USP/NF
• ​Neutralization Reactions (in aqueous and non

aqueous solvents) ​• ​Redox Reactions

• ​Precipitation Reactions

• ​Complexation Reactions
Requirements for a Reaction to be
Utilizable for Titrimetric Analysis
• ​Reaction must proceed to completion. (​K =​ 10​8​)

• ​Reaction must proceed in a stoichiometric

manner.
• ​A suitable end-point detecting device (indicators,
electrodes, etc.) should be available.

• ​For direct titrations, the reaction must be rapid

and a sharp end point must be discernible.
Methods of Making a Reaction to
Proceed to Completion
• ​Formation of a slightly dissociated substance as a
reaction product.
• ​Removal of one or more of the products of the
reaction as a gas.
• ​Removal of one or more of the products of the
reaction as a precipitate.
• ​Removal of one or more of the products of the
reaction as a complex ion.
• ​Addition of an excess of one of the reactants.

*Regardless of technique, only a negligible

amount of the analyte must remain in the
titration flask, otherwise, the method should be
rejected.
Titrimetric Analysis Based on
Neutralization Reactions
• ​Basic principles, general calculations and
laboratory procedures in titrimetric
methods employing neutralization reactions
 also apply to the other types of reactions.

Neutralization Reactions (Acid-Base

Reactions) ​• ​Products are salts and water
depending on the acid and base used, and
must proceed to or near completion to be of
value in quantitative analysis.
Indicators
• ​Complex organic or inorganic compounds used
to:
a.) determine the end-points in neutralization
reactions.
b.) determine [H​+​] or pH
 c.) indicate that a desired change in pH has been
effected.

• ​Such substances are acids or bases themselves,

capable of existing in two forms of different
colors that are mutually convertible.

• ​There are some situations that require a

combination or mixed indicators. E.g.
Methylene Blue-Methyl Red in the Assay of
KNaC​4​H​4​O​6
Theories on the Color Change of
Indicators
Physicochemical Theory
• ​The color is due to certain ions which causes the
appearance of color when increased and
disappearance of color or appearance of a
different color when decreased.
Organic Theory
• ​The color is due to certain groupings of elements
in a compound, and the change in color is due to
a change in molecular structure.
Colloidal Theory
• ​Indicators form colloidal solutions and the
change in color is based on the change in the
particle size of the colloidal particles.
Rules for the Use of Indicators
1.) Three drops of the indicator solution should be
added unless otherwise directed.
2.) When strong acid is to be titrated with strong
base or when a strong base is to be titrated with
a strong acid, MO, MR or Pp maybe used.
3.) When a weak acid is to be titrated with a strong
base, Pp must be used.
4.) When a weak base is to be titrated with a strong
acid, MO or MR must be used.
5.) Weak acids should never be titrated with weak
bases and vice-versa.
6.) The appearance of color is more observable than
to the disappearance, hence, titration should
always be towards the production of a color as
much as possible.
Indicators: Test for Sensitivity
• ​Done by adding 0.15mL of indicator solution
to CO​2​-free distilled water and titrating the
resulting solution with 0.02N alkali or acid.

• ​Upon addition of 0.25mL of standard acid or

alkali, the characteristic color should
develop.
Standard Solutions
Expressed in terms of:
• ​Normality or the number of equivalents of
solute/L or mEq of solute/mL of solution
• ​Molarity or the number of moles of solute/L of
solution; can be converted to N by multiplying M
with the number of equivalents.

• ​Molality or the number of moles of solute/kg of

solvent.

*Normality is expressed to the fourth decimal

place while molarity and molality are usually
expressed to the second decimal place unless
otherwise specified.
Example
Calculate the M of a H​2​SO​4​solution prepared by
 dissolving 4.903g of the acid to make 1L of the
solution. Convert this value to N.
M = wt/MW/L
= ​4.903g__
98.06g/mol
1L
= 0.05M
N = M x no. of equiv. = 0.05 x 2 = 0.1N
Verify N:
wt (g) = V x N x GmEW/mEq
N = _​_wt.__​ ​ ​4.903g​ ​ ​0.1N ​V x mEq 1000mL
x 0.04903g/mEq
Calculations in Volumetric Analysis
• ​Purities of samples as determined by official
assay methods are expressed by %w/v, %w/w
and % v/v.
E.g.
A 50mL sample of Ca(OH)​2​solution required
19.5mL of a 0.1050N HCl solution to neutralize it.
Calculate the amount of Ca(OH)​2​in the sample.
Ca(OH)​2 +​ 2HCl ​ ​CaCl​2 +​ H​2​O
74.08

wt(g) = V x N x mEq
= 19.50mL x 0.1050N x 0.03704g/mEq
= 0.076g Ca(OH)​2 per
​ 50mL sample
Calculations in Volumetric Analysis
 Hence:
g/100mL = ​19.50mL x 0.1050N x 0.03704g/mEq​ = __​Xg​__
50mL 100mL

%P = ​19.50mL x 0.1050N x 0.03704g/mEq x

100mL
50mL

= 0.1517%
Calculations in Volumetric Analysis
If the titer value is given (for %w/v

problems):

A 50mL sample of Ca(OH)​2​solution required

24.96mL of a 0.1668N HCl solution to
neutralize it. Calculate the percent purity of
Ca(OH)​2​in the sample. Each mL of 0.1N HCl
is equivalent to 3.704mg of Ca(OH)​2​.
Normality Factor: 0.1668N/0.1N = 1.668 ​%P
= ​24.96mL x 1.668 x 0.00374g/mL x 100
50mL
= 0.31%
Calculations in Volumetric Analysis
If the titer value is given (for %w/w
problems):

A 4.05g sample of Ca(OH)​2​solution required

24.96mL of a 0.1668N HCl solution to
neutralize it. Calculate the percent purity of
Ca(OH)​2​in the sample. Each mL of 0.1N HCl
is equivalent to 3.704mg of Ca(OH)​2​.

Normality Factor: 0.1668N/0.1N = 1.668

%P = ​24.96mL x 1.668 x 3.704mg/mL x 100
 4050mg
= 3.81%
Standard Solutions in Neutralization
Reactions
Standard acid solutions are usually HCl or H​2​SO​4​. ​• ​HCl is
preferred when the analyte is capable of forming a
precipitate with H​2​SO​4​.
• ​H​2​SO​4​is preferred in titrating hot solutions of analytes.

Standard alkali solutions are usually NaOH, KOH or

Ba(OH)​2​.
• ​These solutions absorb CO​2​from the air.
• ​NaOH and KOH becomes contaminated with CO​3​2-​’s ​•
Ba(OH)​2​is consumed since the CO​2​is precipitated as BaCO​3​. ​•
Hence, they should be prepared from CO​2​-free distilled H​2​O,
 protected by soda-lime absorption tubes and re
standardized frequently.
Preparation and Standardization of Acid
Solutions
• ​Normal HCl solutions maybe standardized
titrimetrically against anhydrous Na​2​CO​3​,
Tromethamine or standard NaOH or KOH,
or; gravimetrically by precipitation to
AgCl.

• ​Normal H​2​SO​4​solutions maybe standardized

titrimetrically against anhydrous Na​2​CO​3 or
​
standard NaOH or KOH, or; gravimetrically
 by precipitation to BaSO​4​.

• ​If titrimetric methods are employed, methyl

red is used as the indicator.
Key Notes in the Standardization of Acids

• ​The primary standard, anhydrous Na​2​CO​3​is

heated first at 270​o​C for 1h to drive off
moisture that it contains as contaminant
and convert all NaHCO​3​also present as
contaminant to Na​2​CO​3.

• ​The neutralization reaction generates CO​2​,

which could be a source of error, hence it is
 driven off at the “first” end point, and
titration is continued.

• ​Na​2​CO​3​is two equivalents:

2HCl + Na​2​CO​3 ​ ​H​2​O + CO​2​↑ + 2NaCl
Key Notes in the Standardization of Acids

Hence: MW(Na​2​CO​3​): 105.99 ​ ​mEq:

0.053

E.g.
If 1.6250g Na​2​CO​3​required 30.20mL of HCl
on titration, what is the N of HCl?
 N = _ ​wt.___ ​ ​1.6250g
V x mEq 30.20mL x 0.053g/mEq

N = 1.0152N
Key Notes in the Standardization of Acids
• ​It is also convenient to standardize HCl against
standard KOH or NaOH.
E.g. What is the normality of a 25mL solution of HCl
if it required 25.20mL of 0.9505N NaOH?
N​1​x V​1 =​ N​2​x V​2
25.20mL x 0.9505N = (N​2​) x 25mL
25.20mL x 0.9505N ​= N​2 ​ ​= 0.9581N 25mL
 • ​More dilute solutions of HCl are conveniently
prepared from 1N HCl, with subsequent re
standardization.
• ​H​2​SO​4​is titrimetrically standardized in the same
manner as HCl. Calculations for N are also
similar.
Preparation and Standardization of Alkali
Solutions
• ​Normal NaOH or KOH solutions maybe
standardized titrimetrically against potassium
biphthalate or standard HCl or H​2​SO​4​solution,
using phenolphthalein as indicator.
• ​NaOH is more commonly used for neutralization
reactions, while KOH is more used for fat
 constants determinations.

Key Notes:
• ​An excess of NaOH is weighed for preparation,
since it is very hygroscopic.
• ​Prepared solutions should be treated with
Ba(OH)​2​in order to precipitate soluble
carbonates from Na​2​CO​3​.
Key Notes in the Standardization of Alkali
Solutions

• ​The prepared solutions must be tightly

stoppered with a fitted soda-lime
tube.
 • ​Solutions with carbonates are not
suitable for titration using
phenolphthalein as indicator,
instead, methyl orange is used.

• ​KHC​8​H​4​O​4​is one equivalent:

NaOH + KHC​8​H​4​O​4 ​ ​KNaC​8​H​4​O​4 +​ H​2​O
Key Notes in the Standardization of Alkali
Solutions
Hence: MW(KHC​8​H​4​O​4​): 204.18 ​ ​mEq: 0.20418
E.g.
If 24.15mL of NaOH solution were required in the
titration of a 4.9651g of KHC​8​H​4​O​4, what
​ is the N
of the NaOH solution?

N = ​4.9651g​ ​ ​= 1.0068N
24.15mL x 0.2042g/mEq

• ​More dilute solutions are also prepared from 1N

solutions of the alkalis.