[Espectrofotometria] Análise de AAS por método FIA

Flow injection spectrophotometric determination of
acetylsalicylic acid in tablets after on-line
microwave-assisted alkaline hydrolysis
Airton Vicente Pereira, Clezio Aniceto and Orlando Fatibello-Filho*
Grupo de Quı´mica Analı´tica, Departamento de Quı´mica, Centro de Cieˆncias Exatas e de
Tecnologia, Universidade Federal de Sa˜o Carlos, Caixa Postal 676, CEP 13.560-970, Sa˜o Carlos,
SP, Brazil. E-mail: doff@power.ufscar.br
The proposed method is based on the on-line
microwave-assisted alkaline hydrolysis of acetylsalicylic
acid (ASA) to salicylic acid (SA) that reacts with FeIII to
form a complex that absorbs at 525 nm. Samples merged
with NaOH were passed continuously through a domestic
microwave oven in order to accelerate the hydrolysis of
ASA. Under the best analytical conditions, the linearity of
the calibration equation for ASA ranged from 25 to 250
mg ml21. The precision for ten successive measurements
of 200 mg ml21 ASA presented a relative standard
deviation of 0.40%. The detection limit was 4.0 mg ml21
and recoveries of 99.1–101.0% were obtained for ASA. No
interference was observed from the common excipients of
tablets and other active substances such as ascorbic acid
and caffeine. The proposed FI method is adequate for a
large number of samples because it is not time consuming
and permits the determination of ASA in 90 samples per
hour.
Keywords: Acetylsalicylic acid; flow injection;
microwave-assisted hydrolysis; spectrophotometry
Acetylsalicylic acid (ASA) is widely used in the relief of
headaches, fever, muscular pains and inflammation due to
arthritis or injury. In solution, the rate of decomposition of ASA
to salicylic acid (SA) is dependent on the pH. At pH 11–12,
ASA is immediately hydrolysed; at neutral and acid solution
(pH 4–8), the hydrolysis rate is slow, and the maximum stability
is attained at pH 2–3.1
The conventional back-titration method2 for ASA determi-
nation is simple and economical, but requires heating over
reflux for 10 min. It has been replaced by HPLC in the more
recent editions of USP.3 UV–VIS spectrophotometry,4–6 fluori-
metry,7,8 amperometry9 and HPLC10–13 methods were reported
for the determination of ASA in pharmaceuticals. HPLC is
preferred over other methods because of the possibility of
simultaneous determination of ASA and SA. However, this
technique is time-consuming and requires sophisticated equip-
ment. Juhl and Kirchhoefer14 developed a semiautomated-UV
detection method for determination of ASA in tablets but a
complex system was used because extraction with chloroform
was necessary. 
The FeIII–salicylate reaction has been used for quantitative
determination of SA in ASA samples and appropriate condi-
tions for the reaction were established. The maximum colour
intensity was obtained at pH 2.5–3.5.15 Lopes-Fernandez
et al.16 proposed an asymmetrical FIA with dual injection for
the simultaneous determination of SA and ASA, which is on-
line hydrolysed to SA in a longer channel and two peaks were
obtained by complexation between FeIII and SA and the
resulting coloured product was measured at 520 nm. The linear
range for ASA varied from 300 to 1800 mg ml21 and 30 samples
were analysed per hour.
Microwave oven pre-treatment of samples has gained
widespread application in different areas and samples.17–20
However, few applications in pharmaceutical analysis have
been reported.21 FIA combined with microwave-assisted alka-
line hydrolysis has been applied to the spectrophotometric
determination of paracetamol in pharmaceuticals.22 On-line
microwave-assisted alkaline hydrolysis of vitamin A to retinol
and its detection at 325 nm was also reported.23
This paper reports the application of a FI spectrophotometric
method for determination of ASA using a microwave-assisted
hydrolysis incorporated in the system in order to minimize the
time of analysis and increase the sensitivity of the method. In
the method presented, it is unnecessary to perform two
determinations, one before and one after hydrolysis, to obtain a
value for the ASA concentration in the samples. The proposed
method is based on the on-line microwave-assisted alkaline
hydrolysis of acetylsalicylic acid to salicylic acid that reacts
with FeIII in acid medium to form a complex that absorbs at 525
nm.
Experimental
Apparatus
The flow injection manifold is shown in Fig. 1. A Panasonic 600
W (Manaus, Brazil) model NN 5556 B domestic microwave
oven equipped with a magnetron of 2.450 MHz was used. A
twelve-channel Ismatec (Zurich, Switzerland) model 7618-50
peristaltic pump supplied with Tygon pump tubing was used to
pump all solutions. The manifold was constructed with
polyethylene and PTFE tubing (0.8 mm id). Sample and reagent
solutions were injected manually into the carrier stream using a
laboratory-constructed three-piece injector–commutator made
of Perspex, with two fixed side bars and a sliding central bar,
that is moved for sampling and injection. A Femto (Sa˜o Paulo,
Brazil) spectrophotometer model 435 equipped with a glass
flow-cell (optical path 1.0 cm) was used for the absorbance
measurements. Peaks were recorded using a Cole Parmer
(Chicago, IL, USA) two-channel strip-chart recorder model
1202-0000.
Reagents and solutions
All reagents used were of analytical-reagent grade and all
solutions were prepared with water obtained from a Millipore
(Bedford, MA, USA) Milli-Q system (model UV Plus Ultra-
Low Organics Water). 
A stock solution of ASA (2.0 mg ml21) was prepared by
dissolving 500 mg of ASA (Synth) in 250 ml of water. Solutions
of desired concentrations were obtained by diluting the stock
solution with water. All solutions to be analysed were prepared
just before injection into the FIA system in order to avoid ASA
hydrolysis to SA.
The solution containing 0.50% (w/v) ferric nitrate in 0.4
mol l21 nitric acid was prepared by adding Fe(NO3)3·9H2O
Analyst, May 1998, Vol. 123 (1011–1015) 1011
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(Riedel, Hannover, Germany) and an appropriate volume of
concentrated nitric acid to a 500 ml calibrated flask and diluting
to volume with water.
Methods
Analysis of pharmaceutical samples
To prepare commercial samples, a known number of tablets
were ground to a fine power and an accurate mass correspond-
ing to about 500 mg of ASA was transferred to a 250 ml
Erlenmeyer flask and stirred with about 200 ml of water. These
solutions were filtered through a filter paper into a 250 ml
calibrated flask and made up to volume with water. This
solution was used for determination after dilution with water to
the desired concentration. A volume of 250 ml of sample was
injected immediately into the carrier stream to prevent errors
due to the conversion of ASA into SA. 
Reference method
In order to compare the results obtained by the FI procedure, the
back-titration method described for aspirin tablets in the British
Pharmacopoeia2 was carried out with minor modifications. An
accurate amount of powder from the tablets was treated with 0.5
mol l21 NaOH and heated in a microwave oven for 3 min at
lower power level to ensure complete hydrolysis and to avoid
boiling. After cooling, the solution was titrated with standard-
ized 0.501 mol l21 hydrochloric acid solution, using phenol-
phthalein as indicator.
Flow injection procedure
The flow injection system for on-line ASA hydrolysis is shown
in Fig. 1. When the central bar of the injector is moved to the
injection position, sample (L1, 250 ml) and R1 reagent (0.2
mol l21 NaOH; L2, 250 ml) are injected as individual zones into
the water carrier streams (C1 and C2; both flowing at 3.4
ml min21) which merged downstream synchronously. At
confluence point x, the water carrier streams merged so that
alkaline hydrolysis of ASA occurs in the PTFE tube reaction
coil B1 (200 cm, 0.8 mm id) placed inside the microwave oven
turned on at the maximum power level (600 W). For