Quality Control 1

Post Laboratory
Discussion
Exercises 3-
9
 Titrimetric Analysis

Determination of the volume of a

solution of known concentration
required to complete a chemical
reaction with a substance being
analyzed.
Also known as Volumetric
analysis.
 Definition of Terms
Analyte
Chemical substance being anlyzed

Titrant
Solution added to react with the substance
being analyzed

Indicator
Organic compounds used to determine the
hydrogen-ion concentration and indicate a
change in pH
 Definition of Terms
End point
A sudden change in the property of
the reaction mixture

Primary standard
A substance of known purity

Secondary standard
May be used in the standardization
of a solution
 Definition of Terms
Standardization
Determination of the concentration of a
solution
Titration
Act of measuring the volume of the
titrant used in the assay
Equivalence point
Theoretical point at which equivalent
amounts of each have reacted
 Definition of Terms
Equivalent
Defined such that one equivalent of one
material will react exactly with one
equivalent of another.

Standard solution
Also known as volumetric solution or
titrant
Solution of known concentration
 Definition of Terms
Molarity
Defined as the number of moles of
solute per liter of solution
Normality
Number of equivalents of solute per liter
of solution
Titer
Weight of a substance chemically equivalent
to 1 mL of a standard solution
 Types of Titration

Direct

Residual

Blank
 Volumetric Apparatus

Two types
Made to deliver a definite volume of
liquid
Made to contain a definite volume of
liquid
Unit of Capacity is in millilter (mL).
 Sources of Error in the Use of
Volumetric Apparatus

Rinse water adhering to the apparatus

Grease films and dirty apparatus
Drainage of the liquid adhering to the vessel wall
Parallax should be avoided
Temperature variations
Air bubbles
Heat
Salts causing change in temperature
 Requirements for Titrimetric
Analysis
Reaction must be complete
Must have an end-point detecting
device (indicator)
Must be rapid
Must have a sharp end-point
 Indicators

To determine end-points in
neutrlization processes

To determine hydrogen-ion
concentration

To indicate that a desired change in

pH has been achieved
 Indicators

Rules in use of indicators

Use 3 drops
Strong acid strong base
Methyl red, methyl orange,
phenolphthalein
Weak acid strong alkali
Phenolphthalein
 Indicators

Rules in use of indicators

Weak base strong acid
Methyl red
Weak acid should never be titrated with
weak base or vise versa
Appearance of color is more
observable
 Mixed Indicators

Methylene blue Methyl red

Xylene cyanol Methyl ornage
Bromocresol green Methyl red
Bromocresol green chlorophenol
red
Cresol red thymol blue
Thymol blue - phenolphthalein
 Standard Solutions
Standard Acid
Hydrochloric Acid
Sulfuric Acid

Standard Base
Sodium hydroxide
Potassium hydroxide
Barium hydroxide
 Standardization

V x N = wt. of 1 std.
mEq wt. of 1 std.
 Formulas used in Volumetric
Analysis
% = V x N x mEq wt x100
wt (g)
% = V x N.F. x Titer x 100
wt (mg)
Content/tab = V x N x mEq. Wt.
x100
wt. per tab
% = content per tab
x100 labelled
amount
 Formulas used in Volumetric
Analysis

Residual titration
% = [ (V x N) (V x N) ] x mEq wt x100
wt (g)
% = [ (V x NF) (V x NF) ] x Titer x100
wt (mg)
 Exercise # 3 - Preparation and
Standardization of 0.1N Sulfuric
acid Solution

Exercise # 4 - Content Uniformity Test for

Sodium Bicarbonate Tablets
Exercise
#3:
Volumetric Solution:
0.1N Sulfuric acid solution
Primary Standard:
Sodium carbonate, anhydrous
Indicator:
Methyl red, TS
End point:
Faintly Pink

What is the reaction involved in the exercise?

H2SO4 + Na2CO3 Na2SO4 + H2O
+ CO2
Exercise #3:
Procedures
PREPARATION:
1. Using a pipette, add slowly 0.32mL sulfuric acid CP to
enough water in a 100mL volumetric flask.
2.Allow to cool to room temperature.

STANDARDIZATION:
3. Weigh accurately 0.15g g primary standard anhydrous
sodium carbonate that has been previously heated at 270C for 1
hour.
4.Dissolve in 75mL distilled water and add 2 drops methyl red TS. 3.Add
the prepared acid slowly from a buret, with constant stirring,
until the solution becomes faintly pink.
4. Heat the solution to boiling, cool, and
continue the titration until faintly pink.
5. Heat again, cool and titrate further as necessary until the pink color
is no longer affected by continued boiling.
 Data Trial 1

Given the Weight of anhydrous sodium 0.25g

carbonate
following
Before boiling
data, what
Final reading of H2SO4 14ml
would be
Initial reading of H2SO4 0ml
the ?
Volume of H2SO4 used
normality of
the sulfuric After boiling
acid Final reading of H2SO4 19ml
solution? Initial reading of H2SO4 14ml
Volume of H2SO4 used ?
Total Volume of H2SO4 used ?
Normality of H2SO4 ?
Exercise
#4:
Volumetric Solution:
0.1N Sulfuric acid solution

Primary Standard:
Sodium bicarbonate

Indicator:
Methyl red, TS

End point:
Faintly Pink
Exercise #4:
PROCEDURES:
1. Weigh 20 sodium bicarbonate tablets and determine their
average weight. Distribute the tablets so that each group will
have enough for two trials.
2.Weigh each tablet and powder finely in a mortar.
3.Transfer the powdered tablet to an Erlenmeyer flask.
4. Add 20mL distilled water to the mortar and add the washings
to the Erlenmeyer flask. Repeat the washing with another
10mL of distilled water. Combine the washings in the flask
and mix well.
5.Add 3 drops methyl red TS.
6.Titrate with 0.1N sulfuric acid until a faint pink color appears.
7.Heat the solution to boiling, cool, and continue the titration until
faintly pink.
8.Heat again, cool and titrate further as necessary until the pink color
is no longer affected by continued boiling.
Titer Statement:
Each mL of 0.1N sulfuric acid is equivalent to 8.401mg
of sodium bicarbonate

USP requirement:
Sodium bicarbonate tablets contains not less than 95% and
not more than 105% of the labeled amount of sodium
bicarbonate.

Content Uniformity requirement:

content of each of the 20 tablets is with in the limits of
NLT 85% and NMT 115%
 Data Trial 1

Given the Weight of anhydrous sodium 0.638g

carbonate
following
Before boiling
data, what
Final reading of H2SO4 25ml
would be the
Weight of Initial reading of H2SO4 0ml
Volume of H2SO4 used ?
pure
After boiling
NaHCO3 per
Final reading of H2SO4 46ml
tablet and
the %label Initial reading of H2SO4 25ml
Volume of H2SO4 used ?
claim if the
Total Volume of H2SO4 used ?
product 0.1N
Normality of H2SO4 used
claims it to be
650mg? Weight of pure NaHCO3 per tablet ?
%label claim ?
 PREPARATION
AND
STANDARDIZATION
OF ACID
AND ALKALI
SOLUTION
 The standard acid solution used in
acidimetry and alkalimetry are usually prepared
from hydrochloric or sulfuric acid.
Either acid may be used in most titrations,
but hydrochloric is preferable than sulfuric acid in
the titration of compounds that yield a precipitate
with the latter, such as barium hydroxide, and
sulfuric acid is preferable in hot titrations, since
there would be danger of loss of hydrochloric acid
due to volatilization.
 The standard alkali solutions commonly used
are sodium hydroxide, potassium hydroxide, and
barium hydroxide.
These solutions absorb carbon dioxide from the
air; thereby changing rapidly in concentration.
Sodium and potassium hydroxide may become
contaminated with carbonates that impair their
usefulness because of the liberation of carbon
dioxide during acid-alkali titration.
 Barium hydroxide solutions remain free from
carbonates, since absorbed carbon dioxide
is this
precipitated as insoluble barium carbonate;
however, decreases the concentration of barium
hydroxide in the solution.
Alkali solutions should be prepared carbonate-
free, and they should be protected from carbon
dioxide by means of soda-lime absorption tubes.
All alkali solutions should be re-standardized
frequently.
 Acid Solutions

Normal hydrochloric acid solution may be standardized

titrimetrically against pure sodium carbonate or standard
solution of sodium hydroxide which has been recently or
standardized, gravimetrically by precipitation of an
equivalent amount of silver chloride.
The standardization of sulphuric acid solution can be
done by titration against sodium carbonate or against normal
sodium hydroxide solution using phenolphthalein as an
indicator.
 Alkali Solutions
Solutions of sodium hydroxide or potassium hydroxide
may be standardized by use of a standard solution of
hydrochloric or sulphuric acid as a secondary standard, or
potassium bipthalate as a primary standard.
 ACID SOLUTIONS ALKALI SOLUTIONS
HYDROCHLORIC ACID SODIUM HYDROXIDE
PRIMARY STANDARD
SODIUM CARBONATE AND POTASSIUM
SECONDARY STANDARD HYDROXIDE
SODIUM HYDROXIDE SOLN. PRIMARY STANDARD
GRAVIMETRICALLY
POTASSIUM
SILVER CHLORIDE
BIPTHALATE
SECONDARY
SULFURIC ACID STANDARD
PRIMARY STANDARD HYDROCHLORIC ACID
SODIUM CARBONATE
SOLN.
SECONDARY STANDARD
SULFURIC ACID SOLN
NaOH SOLN./KOH SOLN.
GRAVIMETRICALLY
BARIUM SULFATE
INDICATOR
PHENOLPHTHALEIN
INDICATORS:
Usually a chemical which changes color at a very
near the point in the titration where equivalent
quantities of analyte and titrant has reacted.
Complex organic compounds used:

To determine the end point in neutralization

processes
To determine hydrogen-ion concentration [H+]
or OH.
To indicate a desired change in pHhas
been effected.
COMMONLY USED pH INDICATORS
INDICATOR ACID BASE
MALACHITE GREEN YELLOW GREEN
METHYL YELLOW RED YELLOW
BROMOPHENOL BLUE YELLOW BLUE
METHYL ORANGE PINK YELLOW
BROMOCRESOL YELLOW BLUE
GREEN
METHYL RED RED YELLOW
BROMOCRESOL YELLOW PURPLE
PURPLE
BROMOTHYMOL BLUE YELLOW BLUE
PHENOL RED YELLOW RED
CRESOL RED YELLOW RED
THYMOL BLUE YELLOW BLUE
PHENOLPHTHALEIN COLORLESS RED
THYMOLPHTHALEIN COLORLESS BLUE
 EXERCISE 5
PREPARATION AND
STANDARDIZATION OF
1N SODIUM
HYDROXIDE
PRIMARY STANDARD:
POTASSIUM
BIPHTHALATE

INDICATOR:
PHENOLPHTHALEIN
T.S.

END POINT:
FAINT PINK
 Solutions of sodium hydroxide or potassium hydroxide
may be standardized by use of a standard solution of
hydrochloric or sulfuric acid as a secondary standard and
potassium bipthalate as a primary standard.

Carbon dioxide free water is prepared by boiling water.

It is important to use carbon dioxide free water in the

preparation of 1N NaOH in order to prevent the formation
of carbonates in sodium hydroxide caused by carbon
dioxide.

The solution is preserved in a tightly stoppered bottle fitted

with a soda-lime tube to protect it from the carbon dioxide
of the air.
Procedures:
PREPARATION:
1. Dissolve 29.5g sodium hydroxide pellets in 100mL carbon
dioxide- free water.
2.Cool the solution to room temperature and filter if turbid.
3. Transfer it in a 500mL volumetric flask and add
enough carbon dioxide-free water to volume.

STANDARDIZATION:
4. Weigh accurately 5g potassium biphthalate, previously
crushed lightly and dried at 120C for 2 hours.
5.Dissolve in 75mL carbon dioxide-free water.
3.Add 2 drops phenolphthalein TS.
4.Titrate with the sodiumhydroxide solution until it
produces a permanent faint pink color.
Chemical Reaction:

KHC8H4O4 + NaOH KNaC8H4O4 + H2O

Titer Value:
Each 1mL of 1N NaOH is equivalent to
204.23g of potassium biphthalate.

Normality Value:
N = weight of KHC8H4O4
mL NaOH x meq(0.20423)
PROBLEM
SOLVING:
In the standardization of sodium hydroxide solution, the
primary standard used was 0.67g potassium biphthalate and
it used up 25.3mL of the solution. What is the
concentration (N) of sodium hydroxide solution?

Answer: 0.1297N or 0.1N

PROBLEM
SOLVING:

What weight of 98.5% potassium

bipthalate is equivalent to 50mL 0.1 NaOH?

Weight of potassium biphthalate = 1.0367 g

PROBLEM
SOLVING:
If 35mL NaOH were found to be equivalent to
40ml H2SO4 solution, and 25 ml of the NaOH
solution were required in the titration of 0.5325g
pure potassium bipthalate, what weight of barium
sulfate could be produced from 42 ml sulfuric acid
solution.
 EXERCISE 6
PREPARATION AND STANDARDIZATION OF
1N SULFURIC ACID

PRIMARY STANDARD
SODIUM CARBONATE

INDICATOR
METHYL RED

END POINT:
FAINT PINK
PREPARATION OF 1N SULFURIC ACID

The standardization can also be effected by titration

against normal sodium hydroxide solution using
phenolphthalein as an indicator.
It may also be standardized gravimetrically by
precipitation and weighing an equivalent amount of
barium sulfate.
Standard solutions of sulfuric acid
preserved in
tightly stoppered, alkali free bottles do not
deteriorate.
 Procedures:
PREPARATION:
1. Using a pipette, add slowly 15mL sulfuric acid CP to enough water
in a 500mL volumetric flask.
2.Allow to cool to room temperature.

STANDARDIZATION:
3. Weigh accurately 1.5g g primary standard anhydrous
sodium carbonate that has been previously heated at 270C for 1
hour.
4.Dissolve in 100mL distilled water and add 2 drops methyl red TS. 3.Add
the prepared acid slowly from a buret, with constant stirring,
until the solution becomes faintly pink.
4. Heat the solution to boiling, cool, and
continue the titration until faintly pink.
5. Heat again, cool and titrate further as necessary until the pink color
is no longer affected by continued boiling.
SULFURIC ACID

Sulfuric acid is a diprotic acid because it

contains 2 hydrogen atoms per
molecule capable of dissociating in
water.

CHEMICAL
REACTION:
Na2CO3 + Na2SO4 + H20
H2SO4 + CO2
PROBLEM SOLVING:

If 25mL sulfuric acid solution were required

in the titration of 0.3592g of pure sodium carbonate,
what is the normality of the solution?
PROBLEM SOLVING:

Strength of acids:
The strength of concentrated acids (official) are
expressed as % w/w, while diluted acids are expressed as
w/v. Consider the specific gravity of conc. Acids in the
calculations.

If sulfuric acid (95%) has a specific gravity

of about
1.83 at 250C, how many grams of H2SO4 will be
contained in 45 mL sulfuric acid.
SOLUTION:

Given: -Specific gravity: 1.83

Volume: 45 ml
Purity: 95%

g= 1.83 X 45 mL X 0.95

g= 78.23g
 EXERCISE 7
PREPARATION AND
STANDARDIZATION OF
1N HYDRCHLORIC
PRIMARY STANDARD: ACID
SODIUM CARBONATE

INDICATOR:
METHYL RED T.S.

END POINT:
FAINT PINK
 Sodium carbonate usually contains varying
amounts of moisture and sodium bicarbonate. When a
sample heated to 270 C, the moisture is driven off and
the NaHCO3 is converted to Na2CO3.

NaHCO3 Na2CO3 + H20 + CO2

The carbon dioxide generated as a result of the

neutralization reaction renders the solution acidic and
introduces an error if not removed.
 Hence, after the first end point is
reached the

solution is boiled to rid it of CO2

(the solution turns yellow after boiling), and the

titration continued to the point where 1 drop of

titrant produces a perceptible color change.

Na2CO3 + 2HCl 2NaCl +

H2O + CO2
TITER VALUE:
1mL 1N HCl is equivalent to
52.99mg of anhydrous sodium carbonate

Normality Calculations:
N = weight of sodium carbonate
mL used X meq

N = 1.5g
28 x 0.05299
N = 1.01
PROBLEM SOLVING:
Homework

If 30 ml HCl were required in the titration of a

0.8560g sodium carbonate, what weight of the
following pure reagents would be needed to
neutralize 30ml of the hydrochloric acid solution.
A.NaHCO3
B. KOH
C. CaO
Ba(OH)2
ACIDIMETRIC
ANALYSIS
ACIDIMETRY
The direct residual titrimetric analysis of bases
or using accurately measured volume of acid, is
an
supplied in the analytical control of a considerable
number of official substances, both oragnic and
inorganic.

DIRECT TITRATION
Conducted by introducing a standard acid solution
gradually from a buret into a solution of the base being
assayed until chemically equivalent amounts of each
have reacted as shown by some changes in the
properties of the mixture.
RESIDUAL TITRATION:

Used whenever the end point of a direct titration

deviates appreciable from the stoichiometric points
for some reasons like when the basic sample is
insoluble in water and the rate of its reaction with the
standard acid is relatively slow.
The sample is treated with an amount of standard
acid known to be in excess and is subsequently
titrated wih a standard base.
the amount of the standard acid which is chemically
equivalent to the basic sample can be calculated
simply by subtracting from the total amount of
standard acid employed, the amount of acid
neutralized by the standard base in the back titration.
SAMPLES FOR DIRECT TITRATION METHODS:
Sodium Bicarbonate
Sodium Hydroxide
Sodium Salicylate Tablets

SAMPLES FOR RESIDUAL TITRATION

METHODS:
Zinc Oxide
Potassium Sodium Tartrate
Methenamine
Milk of Magnesia
Ammonium Chloride Injection
 EXERCISE 8
ASSAY OF ZINC OXIDE
TITRANTs
1N SULFURIC ACID
1N SODIUM HYDROXIDE

INDICATOR
METHYL ORANGE

END POINT:
FAINT PINK TO YELLOW
Assay of Zinc
Oxide:
TITER VALUE:
Each ml of 1N Sulfuric acid is equivalent
to 40.68g of ZnO.
NaOH = 15.5mL H2SO4 = 34.5mL

%ZnO = (34.5 x 1) (15.5 x 1) x0.04068 x 100

1.5
%ZnO = 51.53%

%Zn = (34.5 x 1) (15.5 x 1) x0.0325 x 100

1.5
%Zn = 41.16
How does the assay of Zinc Oxide in the
USP differ from that of zinc oxide
ointment in the past?
Historically the quantitative analysis of
pharmaceutical products containing metal ions such as Al,
Bi, Ca, Mg and Zinc was performed using gravimetric
methods. These procedures were very time-consuming
since they involved precipitation, filtration, washing and
drying or ignition to constant weight.
With the introduction of the analytical reagent EDTA
Direct titration methods were used.
How does the assay of Zinc Oxide in the USP differ
from that of zinc oxide ointment in the past?

ZINC OXIDE RESIDUAL TITRATION

 ZINC OXIDE OINTMENT
COMPLEXATION METHOD (DIRECT TITRATION )
PROBLEM SOLVING:

1. If a 1.3500g sample f zinc oxide, 95% ZnO, were

treated WITH 50Ml OF 1.1250N SULFURIC ACID IN

THE USUAL WAY, What volume OF 0.9800N sodium

hydrxide would be required in the back titration?

PROBLEM SOLVING:
% = 95ZnO meq = 0.04068
mL of acid = 50mL 1.1250N
mL of base=? 0.9800N

95% = (50mL x 1.1250N) (V x 0.9800N) x 0.04068 x 100

1.3500g
95 x 1.3500 = 56.25 09800V x 4.068
128.25 = 228.825 3.9866V
3.9866V = 228.825 128.25
V = 100.575 / 3.986
V= 25.22mL
2. HW: If a 1.500g sample of zinc oxide were treated

with 50mL f 1.25N sulfuric acid in the usual way and

30mL of 1.1098NaOH would be required in the

back titratin, what is the Zn% and %Zn in the

sample?
ALKALIMETRIC
ANALYSIS
 Alkalimetry

Acids and acid salts are analyzed

by titrating with a base of known
purity

Quantity of the acid sample

should be such that 30-40 ml of
base will be consumed
 Alkalimetry

For most inorganic acids

Methyl red and phenolphthalein are
used
For most organic acids
Phenolphthalein is commonly used
Thymol blue, bromothymol blue and
thymolphthalein are also employed
 Direct Alkalimetric Assays
Assay Sample Titrant Indicator
Assay of HCl 1N NaOH Methyl red TS
Hydrochloric
acid
Assay of H3PO4 1N NaOH Thymolphthalein
diluted TS
Phosphoric
acid
Assay of Boric H3BO3 1N NaOH Phenolphthalein
acid TS
Assay of C4H6O6 1N NaOH Phenolphthalein
Tartaric TS
acid
Assay of 2- C8 H10 O2 1N NaOH Phenolphthalein
TS
phenoxyetha
nol
 Det. of hydroxy compounds by
esterification with acetic anhydride

Hydroxy compounds can be

esterified with acetic anhydride
producing acetate ester and acetic
acid

The acetic acid liberated is

equivalent to the hydroxy
compound being acetylated
 Det. of hydroxy compounds by
esterification with acetic anhydride

The blank determination consumes

more base and the difference of
the volumes represent the mount
equivalent to the sample
 Residual titration methods

Include substances that react too

slowly because of poor solubility
which may require a heating or
precipitation procedure

Esters, acid anhydrides, acid

chlorides and aldehydes
 Residual w/ Blank Titration

Assay Sample Titrant Indicator

Assay of C 9 H 8 O4 0.1N H2 Phenolphthal
Aspirin SO4 ein TS
capsule 0.1N NaOH
DIRECT TITRATION METHODS
Examples:
1.Hydrochloric acid
2.Diluted phosphoric acid
3.Boric acid
4.Tartaric acid

RESIDUAL
TITRATION METHODS
Examples:
1.Aspirin
capsules
2.Aluminium acetate
 EXERCISE 9
ASSAY OF BORIC ACID
TITRANT:
1N SODIUM HYDROXIDE

INDICATOR:
PHENOLPTHALEIN

END POINT:
REAPPEARANCE OF PINK COLOR
Procedures:
1. Dissolve about 1.5 g of freshly ignited Zinc Oxide,

accurately weighed, and 2.5 g of ammonium chloride

in 50.0 mL of 1 N sulfuric acid VS with the aid of

gentle heat, if necessary.

2.When solution is complete, add methyl orange TS.

3. And titrate the excess sulfuric acid with 1 N sodium

hydroxide VS.
PROPERTIES of Boric ACID:

Behave s as a very weak monobasic acid

1 mole is equivalent to 61.83g
1mL of 1N sodium hydroxide is equivalent to 61.83mg
of 1meq of H3BO3

CHEMICAL REACTION INVOLVED:

H3BO3 H + BO2- + H20

Why was glycerin used in the assay?

In the presence of glycerin, boric acid behaves like a

sufficiently strong monobasic acid making the

titration with standard alkali feasible with

phenolphtalein as indicator.
%H3BO3 = V x N x meqx 100
wt of sample

Each mL of 1N sodium hydroxide is equivalent to

61.83mg of boric acid.
 HW: What weight of each of the following
substances would be used as a sample so that
35mL of 1N sodium hydroxide would be consumed
in titration to a phenolphthalien endpoint?
A.) acetic acid, CH3COOH
B.) Phosphoric acid, H3PO4
C.) Sodium Biphosphate
D.) Citric Acid, C6H8O7
E.) Tartaric Acid, C4H6O6