ISSN 10619348, Journal of Analytical Chemistry, 2015, Vol. 70, No. 1, pp. 50–54. © Pleiades Publishing, Ltd., 2015.

ARTICLES

Determination of Ibuprofen and Paraben in Pharmaceutical

Formulations Using FlowInjection
and Derivative Spectrophotometry1 ˆ
Sevilay Camalan Türk, Eda Şatana, Hasan Basan*, and Nilgün Günden Gö g er
Gazi University, Faculty of Pharmacy, Department of Analytical Chemistry Etiler, Ankara, 06330 Turkey
*email: basan@gazi.edu.tr
Received June 20, 2012; in final form, May 22, 2014

Abstract—A flowinjection UV spectrophotometric method for the determination of ibuprofen in tablets was
developed. The proposed method was achieved by using a flow cell which was located in a UV spectropho
tometer and a peristaltic pump helped maintaining the carrier solvent, 0.1 M NaOH. During the study, flow
rate, loop volume and the number of injections per hour were 15 mL/min, 193 µL and 100, respectively. The
analytical signal of ibuprofen was linear in the concentration range of 400–1200 µg/mL. The detection limit
and limit of quantification were determined as 27 and 91 µg/mL, respectively. Results for the determination of ibu
profen in tablets, 600 ± 2 mg/tablet (mean ± SD), were in good agreement with the labeled quantities, 600 mg/tab
let. A relatively high recovery value, 100.4 ± 0.6%, proves the accuracy of the proposed method. The spectro
photometric method and reference HPLC method were shown to be comparable when Student’s ttest and
Fisher test were applied to both methods. In addition, a fourth order derivative UV spectrophotometric
method (at 268.8 nm and n = 9) for the determination of ibuprofen and a first order (at 271 nm and n = 1)
derivative UV spectrophotometric method for the determination of paraben in pediatric syrups were devel
oped. Recovery values for the determination of ibuprofen and paraben were 102.4 ± 1.1% and 100.2 ± 2.3%,
respectively.

Keywords: ibuprofen, flowinjection analysis, UV–VIS derivative spectroscopy, HPLC, paraben, pediatric
syrups
DOI: 10.1134/S1061934815010141

1
Ibuprofen, αmethyl4(2methylpropyl)benzene
acetic acid, is a derivative of phenylpropionic acid and is
used as a nonsteroidal antiinflammatory agent. Several
methods have been described for ibuprofen determina
tion in pharmaceutical formulations including chro
matography [1–3], UV spectrophotometry [4–6],
colorimetry [7, 8], electrochemical methods [9, 10],
NMR [11, 12], FT–IR [13] and capillary zone elec
trophoresis [14]. Nowadays, flowinjection analysis
(FIA) has been extensively applied in routine analysis of
pharmaceuticals. Afkhami et al. [15] developed a flow
injection method based on inclusion complexation of
ibuprofen with phenolphthalein–βcyclodextrin.
In this study, a simple, rapid and sensitive flowin
jection UV (FI–UV), spectrophotometric method was
developed for the determination of ibuprofen in tablets.
FI analysis is widely used in routine analysis of pharma
ceuticals and also, to the best of our knowledge, there is
no study in literature describing a FI–UV spectropho
tometric method for the determination of ibuprofen in
tablets without using any pretreatment procedure. In
addition, it was thought that the proposed method
1 The article is published in the original.
would also be a useful technique for the determination
of other pharmaceuticals having similar composition.
Furthermore, a fourth order, at 268.8 nm (n = 9),
and a first order, at 271 nm (n = 1), derivative UV
spectrophotometric methods were proposed for the
determination of ibuprofen and paraben, respectively,
in pediatric syrups. Addition of preservatives to drugs,
especially to syrups, is of great importance due to the
possible presence of microorganisms, which may
transform the drug into inactive compound. Benzoic
acid and esters of phydroxybenzoic acid, known as
hydroxybenzoates or parabens, are common antimi
crobial preservatives added to pharmaceutical formu
lations. For this reason, quantitative determination of
preservatives, especially in syrups, is an important part
of quality control. Although there are some studies de
scribing HPLC methods for the determination of pre
servatives in syrups [16, 17], they are timeconsuming
and highcost compared to derivative UV spectropho
tometric methods. Since ibuprofen and paraben which
are present together in syrups interfere with each oth
er, simultaneous determination of ibuprofen is not
possible in the presence of paraben. In order to solve
this spectral overlap problem, a fourth order derivative

50
 DETERMINATION OF IBUPROFEN AND PARABEN
UV spectrophotometric method was developed for the
determination of ibuprofen in the presence of paraben.
In addition, determination of paraben in the presence of
ibuprofen became possible by using a first order derivative
spectrophotometric method. Throughout these two
studies, determinations were performed without using
any pretreatment procedure.
EXPERIMENTAL
Apparatus. Spectrophotometric analysis was per
formed using Shimadzu UV160A doublebeam UVVIS
spectrophotometer. The flowinjection method was
achieved by using a flow cell located in the UV spectro
photometer (10 mm quartz cell with 0.3 mL internal vol
ume), and Gilson Minipuls 3 four channel peristaltic
pump with Tygon, Pharm Med pinkwhite tubing. Flow
rate and loop volume were 15 mL/min and 193 μL, re
spectively; 100 measurements per hour were conducted.
A Bondelin Sonorex RK 100 H type sonicator was
used. The HPLC system consisted of a model HP series
1050 solvent delivery system with a UVVIS detector set
to 264 nm. A HP ODS hypersil column (10 cm × 3.9 mm
i.d., 5 μm particle size) and a HP 3396 series II integrator
were used. Typical operating conditions include flow
rate (1.5 mL/min), operating temperature (room tem
perature) and injection volume (20 μL).
Reagents and solutions. Ibuprofen was obtained
from Atabay, Turkey. Artril® tablet, 600 mg/tablet (Zen
tiva, Turkey) and Pedifen® pediatric syrup, 100 mg/5 mL
(Atabay, Turkey) were purchased from the local markets
in Turkey. Additives in syrup, paraben and sodium ben
zoate, were purchased from Aldrich. All other reagents
were of analytical grade. Standard solutions of ibupro
fen in the range of 400–1200 μg/mL were obtained by
dissolving appropriate amounts of ibuprofen in 0.1 M
NaOH. Stock solution of paraben was also prepared by
dissolving 25.0 mg of methylparaben and 25.0 mg of
propylparaben in methanol. Standard solutions of para
ben, containing equal amounts of methyl and propylpa
rabens, were prepared by appropriate dilution of the
stock solutions and ranged from 8.0 to 16.0 μg/mL. The
mobile phase used in HPLC was ophosphoric acid–
water–methanol (4 : 246 : 750, v/v/v) and detector
was set to 264 nm.
Determination of ibuprofen in tablets (flowinjec
tion method). The average mass of 10 tablets was deter
mined and then powdered. An amount of powder
equivalent to 20 mg ibuprofen was weighed and trans
ferred to 25 mL volumetric flask and the volume was
adjusted to the mark with 0.1 M NaOH. The solution
was sonicated in an ultrasonicator for 20 min and fil
tered. The absorbance values of the solutions were ob
tained at 265 nm using 0.1 M NaOH as a carrier solu
tion. The ibuprofen content of tablets was calculated
by referring to the calibration curve.
Determination of ibuprofen and paraben in syrups
(derivative spectrophotometric methods). The syrup
JOURNAL OF ANALYTICAL CHEMISTRY Vol. 70
51
volume corresponding to 5 mg of ibuprofen was placed
in a 50.0 mL volumetric flask, diluted to the mark with
methanol and filtered. Fourthorder derivative absor
bance values were measured at 266.8 nm (n = 9). The
ibuprofen content in pediatric syrups was calculated
using the calibration curve drawn using standard solu
tions of ibuprofen ranging from 40 to 360 μg/mL.
For the determination of paraben in pediatric syr
ups, syrup volume corresponding to 5.0 mg of ibupro
fen was placed into a 50.0 mL volumetric flask and di
luted to the mark with methanol. After filtration, first
order derivative absorbance values were obtained at
271 nm (n = 1). By referring to the calibration curve
ranging from 8.0 to 16.0 μg/mL, paraben content in
pediatric syrups was determined.
RESULTS AND DISCUSSION
In the first part of this study, quantitative determi
nation of ibuprofen in tablets was performed using a
FI–UV spectrophotometric method and HPLC as a
reference method. In the second part, ibuprofen and
paraben in pediatric syrups were determined using
fourth order and first order derivative UV spectropho
tometric methods, respectively.
Flowinjection UV spectrophotometric method. Op
timization studies. Several parameters, which were tak
en into consideration in the determination of ibupro
fen, were carefully examined and optimum working
conditions were determined. For that purpose, 56,
120, 138, 193, and 250 μL loop volumes were tested. A
larger loop volume, i.e., a higher sample concentra
tion, lead to more sensitive determination since small
loop volumes resulted in low absorbance values and
wide peaks. However, a longer analysis time was need
ed for each determination. Thus, 193 μL was chosen
as the optimum loop volume. For the optimization of
flow rates, different flow rates, 5, 10, 15, 20 mL/min
were tested. Since it provided higher absorbance values
and sharper peaks, 15 mL/min was chosen as the opti
mum flow rate. To select the best tubing, different sets
of tubes were tested and the one having 2.79 mm i.d.
was selected since it provided optimum flow rate for
the carrier solution. As a result of these optimization
studies, frequency of 100 samples per hour was
reached.
Determination of ibuprofen in tablets. At 265 nm, a
linear relationship was observed between the absor
bance values and concentration of ibuprofen in the
range of 400–1200 μg/mL. The linearity of the cali
bration curve and adherence of the results to Beer’s
law were validated by high value of the correlation co
efficient of the regression equation, r = 0.9998. In ad
dition, the experimental intercept, which was 0.0008,
was very close to the theoretical zero value. A high cor
relation coefficient value and a relatively low standard
deviation (SD) value 2.0, proved the precision of the
proposed method. A standard solution of ibuprofen,
No. 1 2015