Experiment 4

Determination of Aspirin By Indirect Titration

Rombaoa, A.; Balag-ey, K.
College of Science
University of the Philippines Baguio

Abstract
In the experiment, two types of titrations –direct and indirect titration- was
used to determine the concentration of acetylsalicylic acid in a tablet of the
brand Aspilet accurately. Moreover, the titrations were done to determine if
the brand Aspilet conforms to the commercial standard of 90% pure
acetylsalicylic acid in a tablet of commercial aspirin. The data gathered was
calculated through the following statistical tools: mean, normality, standard
deviation, and relative standard deviation. As per the calculations, it was
found that the brand Aspilet had a mean percentage mass of 51% which falls
below the standard concentration.

Introduction

Titration is a type of volumetric method of analysis that is used to identify the amount of
an unknown compound that is present in a given mixture. This method involves the use of a
solution with a known concentration to find the unknown concentration of a given sample and is
performed through the slow addition of a standard solution to an analyte until the reaction is
considered complete (Frank & Pietrzyk, 1979). This experiment however, includes the use of two
types of titration: direct and indirect titration.
Direct titration differs from indirect titration in that direct titration directly measures the
concentration of the unknown compound. Indirect titration, also called back titration, determines
the concentration of the unknown solution through the excess amount of the known compound
(Madhusha, 2017).
In the experiment, direct titration was used to determine the concentration of the HCl
solution. Subsequently, the HCl solution will then be used to titrate the aspirin/ NaOH solution.
While direct titrations are more commonly used, there are situations wherein indirect
titrations are more useful. Such situations include reactions with volatile or insoluble substances,
rapid quantitative reactions that happen only in the presence of excess reagent, and reactions
with substances that decompose upon heating (Shakir et al., 2016). The experiment done falls
under the second category as mentioned above and involves a quantitative reaction with aspirin
(acetylsalicylic acid).
Aspirin is a weak acid derived from two other acids, acetic and salicylic acid. In the
experiment, aspirin is hydrolyzed using a NaOH standard solution. This solution is then titrated
with an HCl solution to determine its concentration.
It is also important to note the presence of an equivalence point which will indicate that
the amount of titrant is chemically equivalent to the amount of analyte in the sample (Skoog,
2014). To show that the equivalence point has been reached, an indicator is needed. In the case
of direct titration, phenolphthalein was the indicator used. On the other hand, in indirect titration,
phenol red was the indicator of choice.
To accurately determine the concentration of aspirin in the brand Aspilet, the
experimenters used mean, normality, standard deviation, and relative standard deviation.
The mean was obtained using the formula:
(eq.1)

Normality was also used as to indicate the concentration of acetylsalicylic acid in the
brand Aspilet. The formula as follows is:

N1V1 = N2V2 (eq. 2)

Also, statistical tools such as standard deviation (SD) and relative standard deviation
(RSD) were used to determine the dispersion of measured data from the calculated mean or
more simply, precision.

(eq. 3,4)

Furthermore, it is also important to note that each of the resulting data can be affected
by the presence of uncertainty in each of the instruments used.

Materials and Methods

The first procedure performed to determine aspirin by indirect titration is the preparation
and standardization of 250 mL of 0.1 N of HCl solution. The volume of concentrated HCl needed
to prepare the 250 mL solution was first calculated. For the standardization, 20.00 mL of the acidic
solution was placed into a 250 mL Erlenmeyer flask and 2-3 drops of phenolphthalein indicator
was added afterwards. This solution was titrated until a faint pink end point was achieved using a
NaOH solution as a standard.
The next part was the analysis of aspirin. First, 0.0951 grams of ground commercial aspirin
was weighed out into a 250 mL Erlenmeyer flask. 50.0 mL of the previously prepared 0.1 N NaOH
solution was added into the flask using a volumetric pipette to minimize the uncertainty of
measurement. The aspirin needed to be hydrolyzed and was done by simmering the solution. In
a 250 mL volumetric flask, the cooled solution was transferred and was diluted with distilled water
until it reached the mark of the flask. the flask was stoppered and was inverted several times to
ensure that the solution was mixed well.
Finally, 50.00 mL of the hydrolyzed aspirin was titrated with the standardized HCl solution
using 2-3 drops of phenol red indicator. A yellow change in the solution indicated the titration’s
end point.
 All glassware used were properly cleaned and dried prior to the experiment.

Results
The first data gathered and calculated was the normality of concentrated HCl which is 12
N. It was also found out that 2.08 mL of HCl was used to prepare 0.1 N of HCl solution.

Trial 1 Trial 2 Trial 3

Volume of HCl titrated 20 mL 20 mL 20 mL
Volume of NaOH used 20.5 mL 20.2 mL 19.8 mL
Normality of HCl (eq/L) 0.103 ± 0.0006 0.101 ± 0.0006 0.099 ± 0.0006
Mean Normality of HCl (eq/L) 0.101 ± 0.01
Relative Standard Deviation 0.140 %
Table 1. Standardization of NaOH Solution
Table 1 shows the volume of HCl titrated and the volume of NaOH used. These values
are needed to calculate the normality of HCl in each trial. The mean normality and the relative
standard deviation are also showed in Table 1.

Trial 1 Trial 2 Trial 3

Volume of aliquot 50 mL 50 mL 50 mL
Volume of HCl used 4.8 mL 4.6 mL 5.1 mL
Mass ASA in sample (g) 0.050 ± 0.0007 0.049 ± 0.0007 0.047 ± 0.0007
% ASA 53% 51% 49%
Mean mass ASA 0.048 ± 0.0007
RSD 0.031%
Mean % ASA 51%
Table 2. Analysis of Sample
As shown in Table 2, the data gathered in the titration of ASA indicates that 0.0951 grams
of ground commercial Acetyl Salicylic Acid was used and analysed. 50 mL of aliquot (ASA and
NaOH solution) was used in all trials. Volume of HCl used indicated in the table shows the amount
that was used before the solution reached the end point. From these data, we were able to
calculate the actual mass and percent concentration of acetylsalicylic acid the Aspilet brand
contains.

Discussion
From the previous experiment, the concentration of NaOH was able to be identified. As
what was stated, back titration uses an excess amount of base with a known concentration where
in this case is therefore the NaOH solution. This was added to the ASA sample, so its actual
concentration can be determined. Afterwards, this solution was titrated with HCl to determine the
amount of unreacted NaOH. This amount is then subtracted from the initial amount of NaOH to
find the actual quantity of NaOH base that reacted with the aspirin. This also yields to the actual
quantity of aspirin in the aliquot.
A. Preparation and Standardization of 0.1 N HCl solution
To prepare 250 ml of 0.1 N HCl solution, it was calculated that 2.08 mL concentrated HCl
was needed. It was then standardized through titration with an unknown concentration of NaOH.
It was computed using the formula below:
𝑁𝑁𝑎𝑂𝐻 − 𝑉𝑁𝑎𝑂𝐻
𝑁𝐻𝐶𝑙 = (eq. 5)
𝑉𝐻𝐶𝑙

The mean normality of HCl was found to be 0.101 ± 0.01 N while the relative standard deviation
of the normalities of HCl was found to have a percentage of 0.140 %. The RSD indicates that the
resulting calculations were precise

Calculations

𝑁𝑁𝑎𝑂𝐻 − 𝑉𝑁𝑎𝑂𝐻
A.Normality of HCl [ 𝑁𝐻𝐶𝑙 = 𝑉𝐻𝐶𝑙 ]

(0.1 𝑁)(20.5 𝑚𝐿)

Trial 1: NHCl = = 0.103 𝑁
20 𝑚𝐿
(0.1 𝑁)(20.2 𝑚𝐿)
Trial 2: NHCl = = 0.101 𝑁
20 𝑚𝐿
(0.1 𝑁)(19.8 𝑚𝐿)
Trial 3: NHCl = = 0.099 𝑁
20 𝑚𝐿

∑𝑛𝑖=1 𝑁𝐻𝐶𝑙 𝑖
B.Mean Normality of HCl [ 𝑥̅𝑁𝐻𝐶𝑙 = 𝑛 ] (e.q.6)

∑𝑛𝑖=1 𝑁𝐻𝐶𝑙 𝑖
𝑥̅𝑁𝐻𝐶𝑙 =
𝑛
(0.103) + (0.101) + (0.099)
𝑥̅𝑁𝐻𝐶𝑙 =
3
𝑥̅𝑁𝐻𝐶𝑙 = 0.101
C.Uncertainties

Unc. NNaOH 2 Unc. of Initial and Final Vol.(burette) 2 Unc. Pipette 2

[ U= 𝑁𝐻𝐶𝑙 ×(√( ) +( ) +( ) ] (e.q.7)
NNaOH VNaOH VHCl

0.0001 2 0.07 2 0.06 2

Trial 1: 𝑈 = 0.103 × √( ) +( ) +( )
0.1 20.5 20.0

U = 0.00056

0.0001 2 0.07 2 0.06 2

Trial 2: 𝑈 = 0.101 × √( ) +( ) +( )
0.1 20.2 20.0

U = 0.00056

0.0001 2 0.07 2 0.06 2

𝑈 = 0.099 × √( ) +( ) +( )
Trial 3: 0.1 19.8 20.0

U = 0.00055

D.Mean Uncertainties [ 𝑥̅ = ∑ Unc. NHCl ] (e.q.8)

3

0.00056 + 0.00056 + 0.00055

𝑥̅ =
3
𝑥̅ = 0.00055

𝑆𝐷
E.Relative Standard Deviation [ 𝑅𝑆𝐷 = × 100% ] (e.q.9)
𝑥̅
𝑆𝐷
𝑅𝑆𝐷 = 𝑥̅
× 100%

0.14
𝑅𝑆𝐷 = × 100%
0.101
RSD = 0.140 %
 B. Analysis of Sample
In contrast to direct titration where the equivalence point is easily distinguished by a change
in color, back titration produces an endpoint that is harder to distinguish. This is because there
is no observable color change and therefore no change in the pH at the equivalence point.
Moreover, the NaOH to acetylsalicylic acid reaction is a weak base to weak acid reaction which
requires the use of indirect titration to be able to determine the amount of acetylsalicylic acid in
the aspirin sample.
The mass of acetylsalicylic acid can be determined via the following formula:

𝐿 𝑜𝑓 𝑠𝑡𝑜𝑐𝑘 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛
𝑚𝑎𝑠𝑠 𝐴𝑆𝐴 = [(𝑁𝑁𝑎𝑂𝐻 𝑉𝑁𝑎𝑂𝐻 ) − ((𝑁𝐻𝐶𝑙 𝑉𝐻𝐶𝑙 ) ( ))] ∗ (𝐸𝑊 𝐴𝑆𝐴)
𝐿 𝑜𝑓 𝑎𝑙𝑖𝑞𝑢𝑜𝑡
(e.q.10)

At the equivalence point, it is also known that: eq ASA = eq NaOH – eq excess NaOH
where eq NaOh is the concentration of NaOH while eq excess NaOH is the concentration of HCl
that is used during direct titration.

Calculations

𝑚𝑎𝑠𝑠 𝐴𝑆𝐴 𝑣𝑜𝑙 𝑠𝑡𝑜𝑐𝑘

A.Mass ASA [ = (𝑁 × 𝑉)𝑁𝑎𝑂𝐻 − (𝑁 × 𝑉)𝐻𝐶𝑙 ( )]
𝐸𝑊 𝐴𝑆𝐴 𝑣𝑜𝑙 𝑎𝑙𝑖𝑞𝑢𝑜𝑡

𝑚𝑎𝑠𝑠 𝐴𝑆𝐴 𝑣𝑜𝑙 𝑠𝑡𝑜𝑐𝑘

Trial 1: = (𝑁 × 𝑉)𝑁𝑎𝑂𝐻 − (𝑁 × 𝑉)𝐻𝐶𝑙 ( )
𝐸𝑊 𝐴𝑆𝐴 𝑣𝑜𝑙 𝑎𝑙𝑖𝑞𝑢𝑜𝑡

𝑚𝑎𝑠𝑠 𝐴𝑆𝐴 0.250 𝐿

= (0.1 × 0.050 𝐿) − (0.103 × 0.02) ( )
9.57 𝑔/𝐿 0.050𝐿
𝑚𝑎𝑠𝑠 𝐴𝑆𝐴
= 0.005 𝐿 − 0.00206(5)
9.57 𝑔/𝐿
𝑚𝑎𝑠𝑠 𝐴𝑆𝐴
= 0.005 𝐿 − 0.0103
9.57 𝑔/𝐿
mass ASA = 0.0053 𝐿 x 9.57 g/L
mass ASA = 0.050721 g
 𝑚𝑎𝑠𝑠 𝐴𝑆𝐴 𝑣𝑜𝑙 𝑠𝑡𝑜𝑐𝑘
= (𝑁 × 𝑉)𝑁𝑎𝑂𝐻 − (𝑁 × 𝑉)𝐻𝐶𝑙 ( )
Trial 2: 𝐸𝑊 𝐴𝑆𝐴 𝑣𝑜𝑙 𝑎𝑙𝑖𝑞𝑢𝑜𝑡

𝑚𝑎𝑠𝑠 𝐴𝑆𝐴 0.250 𝐿

= (0.1 × 0.050 𝐿) − (0.101 × 0.02) ( )
9.57 𝑔/𝐿 0.050𝐿
𝑚𝑎𝑠𝑠 𝐴𝑆𝐴
= 0.005 𝐿 − 0.00202(5)
9.57 𝑔/𝐿
𝑚𝑎𝑠𝑠 𝐴𝑆𝐴
= 0.005 𝐿 − 0.0101
9.57 𝑔/𝐿
mass ASA = 0.0051 𝐿 x 9.57 g/L
mass ASA = 0.048807 g

Trial 3: 𝑚𝑎𝑠𝑠 𝐴𝑆𝐴 = (𝑁 × 𝑉) 𝑣𝑜𝑙 𝑠𝑡𝑜𝑐𝑘

𝑁𝑎𝑂𝐻 − (𝑁 × 𝑉)𝐻𝐶𝑙 ( )
𝐸𝑊 𝐴𝑆𝐴 𝑣𝑜𝑙 𝑎𝑙𝑖𝑞𝑢𝑜𝑡

𝑚𝑎𝑠𝑠 𝐴𝑆𝐴 0.250 𝐿

= (0.1 × 0.050 𝐿) − (0.099 × 0.02) ( )
9.57 𝑔/𝐿 0.050𝐿
𝑚𝑎𝑠𝑠 𝐴𝑆𝐴
= 0.005 𝐿 − 0.00206(5)
9.57 𝑔/𝐿
𝑚𝑎𝑠𝑠 𝐴𝑆𝐴
= 0.005 𝐿 − 0.0099
9.57 𝑔/𝐿
mass ASA = 0.0049 𝐿 x 9.57 g/L
mass ASA = 0.046893 g

∑ mass ASA
B. Mean Mass ASA [ 𝑥̅ = ]
3

∑ 𝑚𝑎𝑠𝑠 𝐴𝑆𝐴
𝑥̅ =
𝑛
(0.050) + (0.049) + (0.047)
𝑥̅ =
3
𝑥̅ = 0.049
 𝑀𝑎𝑠𝑠 𝐴𝑆𝐴 𝑓𝑟𝑜𝑚 𝑎𝑙𝑖𝑞𝑢𝑜𝑡
C.% Mass ASA [ %𝐴𝑆𝐴 = × 100% ]
𝑀𝑎𝑠𝑠 𝐴𝑆𝐴 𝑓𝑟𝑜𝑚 𝑠𝑎𝑚𝑝𝑙𝑒

0.050721
Trial 1: %𝐴𝑆𝐴 = × 100% = 53 %
0.0957

Trial 2: %𝐴𝑆𝐴 = 0.048807 × 100% = 51 %

0.0957

Trial 3: %𝐴𝑆𝐴 = 0.046893 × 100% = 49 %

0.0957

∑ % mass ASA
D.Mean % Mass ASA [ 𝑥̅ = ]
3

(53%) + (51%) + (49%)

𝑥̅ =
3
𝑥̅ = 51%

E. Relative Standard Deviation

𝑆𝐷
𝑅𝑆𝐷 = × 100%
𝑥̅
0.00153
𝑅𝑆𝐷 = × 100%
0.04867

= 0.03143 %

Conclusion
Indirect titration is a method of volumetric analysis that involves the reaction of
the excess of a standard solution with an analyte wherein concentration of said analyte is
determined via titration with a second standard solution. In the experiment, this method was
used to determine the concentration of acetylsalicylic acid in a tablet of the brand Aspilet.
Hydrochloric acid (HCl) was the compound used to titrate the three aliquots (three trials)
used for the analysis of the aspirin sample. Aside from that, HCl was also the compound used to
be able to determine the amount of excess NaOH in the hydrolyzed aspirin. As the calculated
data indicates, the mean percent of acetylsalicylic acid in the Aspilet tables was found to be
51%. The results was found to be not within the standard requirement of acetylsalicylic acid in
commercial aspirin tablets as it falls beneath 90%. The low purity percentage may be due to
factors such as reagent contamination and wrong concentrations. The computed RSD was also
found to be 0.031 % which indicates a precise measurement of data.
Answers to Post Laboratory Questions
1. What would be the effect of a more dilute solution of NaOH on the titration?

A more dilute solution of NaOH used in titration affects the accuracy of the results and
not the reaction between the acid and the standard base. This can be explained by
the fact that titration uses a standard solution that reacts with a known stoichiometry
analyte to the point of equivalence and its accuracy depends on the concentration of
the reagent used.

2. What volume of 1.00 N NaOH is used in the hydrolysis of four 250 mg tablets of aspirin
(90% pure acetylsalicylic acid) if 10.00 mL of 0.0500 N HCl is consumed in the back
titration?

10.5 mL of the 1.00 N NaOH was used in the hydrolysis of the aspirin tablets. It was
determined by performing the following calculations:

𝑀𝑜𝑙𝑎𝑟 𝑚𝑎𝑠𝑠 𝐴𝑆𝐴

[(𝑁𝑁𝑎𝑂𝐻 × 𝑉𝑁𝑎𝑂𝐻 )(𝑁𝐻𝐶𝑙 × 𝑉𝐻𝐶𝑙 )] × × 100%
%𝐴𝑆𝐴 = 2000
𝑀𝑎𝑠𝑠 𝑜𝑓 𝐴𝑠𝑝𝑖𝑟𝑖𝑛

𝑚𝑒𝑞 𝑚𝑒𝑞 180.2

[(1.0 ) (𝑉𝑁𝑎𝑂𝐻 ) − (0.05 ) (10.00𝑚𝑙)] × 2000 × 100%
90% = 𝑚𝑙 𝑚𝑙
1𝑔
𝑚𝑒𝑞 𝑚𝑒𝑞 180.2
[(1.0 𝑚𝑙 ) (𝑉𝑁𝑎𝑂𝐻 ) − (0.05 𝑚𝑙 ) (10.00𝑚𝑙)] × 2000
0.90 =
1𝑔
𝑚𝑒𝑞 𝑚𝑒𝑞
1800 = [(1.0 ) (𝑉𝑁𝑎𝑂𝐻 ) − (0.05 ) (10.00𝑚𝑙)] × 180.2
𝑚𝑙 𝑚𝑙
𝑚𝑒𝑞 𝑚𝑒𝑞
9.99 = [(1.0 ) (𝑉𝑁𝑎𝑂𝐻 ) − (0.05 ) (10.00𝑚𝑙)]
𝑚𝑙 𝑚𝑙
9.99 + 0.5
𝑉𝑁𝑎𝑂𝐻 =
1.0
𝑉𝑁𝑎𝑂𝐻 = 10.5 𝑚𝑙

References

Frank C. W. and Pietrzyk D. J. (1979). Analytical Chemistry Second Edition. 111 Fifth Avenue,
New York, New York, 10003. Academic Press Inc.
Shakir, S.M., Hameed, A.H., & Basim, A. (2016). Quantitative Assay of Aspirin Tablets
[Powerpoint Presentation]. Retrieved from
opharm.uobaghdad.edu.iq/uploads/2016/stages/Assay%20of%20aspirin%20tablets.pdf
Determination of Aspirin using Back Titration. (n.d.). Retrieved on Sept 17, 2018 from
http://www1.lasalle.edu/~prushan/BackTitration-lab4.pdf
Madhusha. (2017 September 25). Difference Between Back Titration and Direct Titration.
Retrieved from http://pediaa.com/difference-between-back-titration-and-direct-titration/