Assay of Aspirin

1. ASSAY OF ASPIRIN
The main methods used in quantitative determination of
ASA either in its pharmaceutical preparations or
powdered pure form are:
1- Spectrophotometric methods:
.
2- Chromatographic methods: such as: GC, TLC, and
HPLC.
3- Titration (volumetric) methods: are very simple and
accurate methods; therefore, these methods are the most
widely used for the quantitative determination of ASA
such as:

2. A- Direct titration method: ASA can be determined
after dissolving it in ethanol by using a standard base as
NaOH as a titrant solution and phenolphthalein (phph)
as an indicator.
B- Back titration method: is one of volumetric
methods which includes the addition of an excess of
standard volumetric sol. to a weight amount of a sample
and then determination for the excess unreacted (no
required or utilized by the sample), then the amount of
volumetric sol. used by the substance is determined.

3. This method is used for:
1- Volatile substances like NH3.
2- Insoluble substances, e.g. CaCO3.
3- Substances which decompose on heating, e.g.
formaldehyde.
4- Substances for which quantitative reaction
proceeds rapidly only in the presence of excess
amount of reagent, e.g. lactic acid & aspirin.

4. Requirements of titration assay reactions:
1- The reaction should be complete and irreversible.
2- Rapid.
3- Endpoint can be easily detected.
4- Can be represented by a chemical equation (to
calculate the chemical factor).
Principle of assay:
ASA is readily dissolved in ethanol and 0.5 N NaOH
solution was then added, the hydrolysis of ASA takes
place when the stoppered solution allowed to stand for
30 min. the excess NaOH volume is titrated with 0.5 N
HCl solution using phph as indicator, the same titration
procedure was repeated except that ASA was omitted
from the solution to serve as a blank.

5. The difference between the vol. of HCl used in both
titrations represents the required amount of NaOH solution
to hydrolyze the ester gp in ASA beside the conversion of
the COOH gp to sod. carboxylate.
The hydrolysis solution must be protected from air
because CO2 causes a color change of the indicator
before the endpoint is reached
[some NaOH  Na2CO3   Vex. NaOH].

6. Also it is necessary to carry blank solution under the
same condition without ASA in order to reduce any
error due to the presence of impurities or to the
condition.
Phph (phenol sulfonphthaleine) indicator is colorless
in acidic media and it changes to pink in basic
solution. pH range is 6.4-8.

7. Procedure:
1. 0.5 N HCl was prepared and standardized with
Na2CO3 using methyl orange as indicator.
2. 0.5 N NaOH was prepared and standardized with
0.5 N HCl using phph as indicator.
3. Dissolve ASA sample in 5 ml ethanol 95 % and
then add 25 ml of 0.5 N NaOH, the container of the
mixture was stoppered and allowed to stand for ½
hour to complete the hydrolysis of ASA.
4. 1-2 drops of bromophenol blue (bpb) indicator was
added and the solution was titrated with 0.5 N HCl.
The endpoint is pink  colorless.
5. Repeat the same procedure without ASA.

8. Note:
Back titration of the excess alkali is necessary to
carry out a blank experiment without acetyl salicylic
acid.
Heating and cooling of alkaline liquid results in an
apparent changes in the strength of certain indicators
used. This may be due to the absorption of
atmospheric CO2 gas. The CO2 is rapidly absorbed by
the hot sol (NaOH) to form sod. carbonate. In the
back titration , CO2 causes a color change of indicator
before the actual endpoint.

9. Calculations:
V1 of blank – V2 of unk. = V3 of NaOH
[VHCl  VNaOH], [VHCl  VNaOH free], [VNaOH  VASA]
V3 x 0.04504 g ASA = g ASA in our sample
1 mole ASA  2 mole NaOH
180.15 g/ml ASA  2000 ml 1 N NaOH
90.075 g/ml ASA  1000 ml 1 N NaOH
90.075/2 g/ml ASA  1000 ml ½ N NaOH
45.04 g/ml ASA  1000 ml 0.5 N NaOH
45.04/1000 g/ml C9H8O4  1 ml 0.5 N NaOH
0.04504 g/ml C9H8O4  1 ml 0.5 N NaOH

10. Q1/ why we use warm
water in recrystallization
of ASA?
Q2/what is the purpose of
activated charcoal?

11. Q1/what are the substances that
could be used for back titration?
Q2/if the vol. of HCl for unk 20
ml and the vol of HCl of blank
30 ml and we use the HCl and
NaOH 2 N , what the amount of
aspirin ?