Original Articles

RP-HPLC METHOD FOR SIMULTANEOUS DETERMINATION OF

IBUPROFEN AND FAMOTIDINE IN PHARMACEUTICAL DOSAGE FORM
L. Peikova*, M. Georgieva, B. Tsvetkova
Medical University Sofia, Faculty of Pharmacy, Department of Pharmaceutical chemistry,
D2 Dunav str., 1000 Sofia, Bulgaria
Abstract: In this study, reversed phase high performance liquid chromatographic method have been developed and validated for the simultaneous determination of ibuprofen and famotidine in combined pharmaceutical formulation. Separation was achieved with a C8 (250 mm x 4.6 mm, 5 m) column, ambient
temperature with isocratic mode with mobile phase containing acetonitrile and 0.5 M potassium dihydrogen
phosphate buffer pH 2.2 adjusted with ortho-phosphoric acid (25:75). UV detection was performed at 280
nm. The flow rate was 1.2 ml/min. The retention times of ibuprofen and famotidine were found to be 3.19
min and 8.37 min, respectively. The responses were linear (R2 > 0.9999) in the range of 20 160 g/ml for
ibuprofen and 0.68 5.4 g/ml for famotidine. The % recovery for ibuprofen and famotidine was 99.75 and
99.24, respectively. No chromatographic interference from the tablet excipients was found. The results of
the studies showed that the proposed RP-HPLC method is simple, rapid, precise and accurate, which can be
applied for the routine analysis of ibuprofen and famotidine in tablet dosage forms.

Key words: liquid chromatography, validation, ibuprofen, famotidine, tablet dosage form,
quality control

Introduction
The 2-arylproprionic acid derivative, ibuprofen, (RS)2-(4isobutyl phenyl) propionic
acid is a nonsteroidal anti inflammatory drug
(NSAID) which is used in reducing inflammation and pain associated with many diseases like
rheumatoid arthritis, osteoarthritis and related
conditions. Ibuprofen is characterized by a better
tolerability compared with other NSAIDs.
Famotidine is chemically 3-([2-(diaminomethyleneamino) thiazol- 4-yl] methylthio)-Nsulfamoylpropanimidamide. It is commonly applied in the treatment of peptic ulcer disease and
gastro esophageal reflux disease. Famotidine is
histamine H2-receptor antagonist which blocks
the action of histamine on stomach cells and reduces acid production [1, 2].
A fixed dose combined dosage form of ibuprofen and famotidine is indicated for the relief
of signs and symptoms of rheumatoid arthritis
and osteoarthritis and to decrease the risk of developing upper gastrointestinal ulcers. Ibuprofen is helpful in relieving the pain and inflammation associated with arthritis and famotidine
reduces the risk of gastric ulcers which is a side
effect in chronic usage of ibuprofen [3]. The
combination of these two drugs is not official in
any pharmacopoeia.

Extensive literature survey revealed determination of famotidine in dosage form by HPLC

[4-10] and UV-spectrophotometry [11]. Analysis of ibuprofen in both pharmaceutical dosage
forms and blood plasma has been reported by
UV-spectrophotometry [12], capillary zone electrophoresis [13] and HPLC [14, 15]. Simultaneous determination of ibuprofen and famotidine
in combination includes liquid chromatographic
techniques [16-18], UV- spectrophotometry [1921] and thin layer chromatography [22].
The aim of the present study is to develop an
analytical method for simultaneously determination of ibuprofen and famotidine in a tablet formulation containing 400 mg ibuprofen and 13.3
mg famotidine using isocratic reversed phased
liquid chromatographic procedure.
Materials and methods
Reagents and chemicals
Working standards of ibuprofen RS (Purity 100.1)
and famotidine RS (purity 99.92) were provided
by (Sigma-Aldrich). The formulated tablets (label
claim: ibuprofen 400 mg and famotidine 13.3 mg)
were used for analysis. LC-grade acetonitrile and
ortho-phosphoric acid were procured from Merck
(Germany). All other chemical reagents were of
analytical grade.

L. Peikova, M. Georgieva, B. Tsvetkova

PHARMACIA, vol. 61, No. 2/2014

Preparation of reference solutions

For ibuprofen: 16 mg of ibuprofen was accurately weighed and transferred to a 50 ml volumetric flask and volume was made up to the mark with
methanol (Stock solution A - 320 g/ml).
For famotidine: 27 mg of famotidine was accurately weighed and transferred to a 100 ml volumetric flask and volume was made up to 100 ml with
methanol (Stock solution B - 270 g/ml). From Stock
solution B, 5.0 ml was taken into a 50 ml volumetric
flask and volume was made up to 50 ml with methanol (Stock solution C - 27 g/ml).
For mixed standard: The reference solution
was prepared by diluting 5.0 ml of stock solution A
and 2.0 ml of stock solution C with methanol into
a 20.0 ml volumetric flask (80 g/ml ibuprofen and
2.7 g/ml famotidine).
Sample preparation
Tablets working solution was prepared as follows: an accurately weighed quantity of powdered
tablet sample containing an equivalent of 400 mg
ibuprofen and 13.3 mg famotidine were transferred
into 100 ml volumetric flask, then 70 ml methanol
was added. The mixture was sonicated for ten minutes and the volume was made up using methanol,
then the sample was filtered. 2.0 ml of the filtrate
was diluted with methanol into a 100.0 ml volumetric flask to give a test solution containing 80
g/ml ibuprofen and 2.7 g/ml famotidine.

Results and discussion

Method validation
The proposed method was validated with respect
to specificity, linearity, precision, accuracy, limit of
quantitation (LOQ) and limit of detection (LOD).
Specificity
The specificity of the method was determined by
checking the interference of the components against
placebo. No interference was observed for any of the
excipients of both drugs. The Fig. 1 showed typical
chromatogram obtained from analysis of standard solution using the proposed method. The retention time
observed 3.19 min for ibuprofen and 8.37 min for
famotidine permits a rapid assay, which is important
for routine analysis.
Calibration and linearity
To establish the linearity of analytical method, a
series of dilution in the range from 20-160 g/ml for
ibuprofen and 0.68-5.4 g/ml for famotidine were
prepared. All the solutions were filtered through
0.22 m membrane filter prior to use and injected
in chrommatograph. A calibration curves were plotted between the mean peak areas vs. respective concentrations.
Results
and discussion The corresponding linear regression
equation was y=10784x-1320.2 with square of corMethod validation
relation coefficient R2 of 0.9999 for ibuprofen and
The y=18540x-1264.4
proposed method was validated
respectof
to correlation
specificity, linearity,
precision,
with with
square
coeffi2
cientlimit
R ofof
0.9999(LOQ)
for famotidine,
respectively.
accuracy,
quantitation
and limit of detection
(LOD).
Specificity

Limit of quantitation and limit of detection

The limit of quantitation and limit of detection
components
placebo. No
interference
was observed for
any of the excipients
were against
calculated
from
the standard
deviations
and of
the
responses
using a signal-to-noise
bothslopes
drugs. Theof
Fig.
1 showed
typical chromatogram
obtained from analysisratio.
of standard
The LOQs for ibuprofen and famotidine were found
solution using the proposed method. The retention time observed 3.19 min for
to be 2 g/ml and 0.8 g/ml, while the LODs were
ibuprofen
and 8.37 and
min for
a rapid assay, which is important for
0.2 g/ml
0.1famotidine
g/ml,permits
respectively.
The specificity of the method was determined by checking the interference of the

routine analysis.
m V(x10)
Detector A:280nm
3.00
2.75

8.367/883900

Instrumentation and chromatographic conditions

Chromatographic separation was performed on
a modular HPLC system LC-10AShimadzu (Japan) comprising a LC-10A pump, solvent degasser DGU-3A, Rheodyne injector with 20 l loop,
column oven CTO-10A, SPD-M10A UV detector
with fixed wavelength and communication bus
module CBM-10A. Separation was achieved isocratically with a LiChrosorb C8, 250 mm x 4.6 mm,
5 m column eluted with a mixture of acetonitrile
and 0.5 M potassium dihydrogen phosphate buffer
pH 2.5 adjusted with ortho-phosphoric acid (25:75
v/v) as the mobile phase at flow rate of 1.2 ml/
min. The mobile phase was filtered through a 0.45
m membrane filter and degassed. Detection was
carried out by absorbance at 280 nm. The analysis
was carried out at ambient column temperature and
injection volume was 20 l.

3.195/987885

2.50
2.25
2.00
1.75
1.50
1.25
1.00
0.75
0.50
0.25
0.00
0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

9.0

10.0

11.0

m in

Figure
1. Chromatogram obtained
from
analysis
of standard
Fig
1. Chromatogram
obtained
from
analysis
of solution
standard solution
Calibration and linearity
To establish the linearity of analytical method, a series of dilution in the range from 20160 g/ml for ibuprofen and 0.68-5.4 g/ml for famotidine were prepared. All the
solutions were filtered through 0.22 m membrane filter prior to use and injected in

RP-HPLC method for simultaneous determination of Ibuprofen ...

Accuracy
Recovery studies were performed to validate the
accuracy of developed method. To the preanalysed
sample solution, a definite concentration of standard
drug was added and then its recovery was analysed.
The percent recovery for ibuprofen was found to be
99.75 % and for famotidine it was 99.24 %. Results
presented in Table 1 indicated good accuracy and
showed no interference from tablet excipients.
Precision
The precision of the method was evaluated by
performing six independent determinations of the
test sample preparation and calculating RSD (%).
The RSD values measured during assessment of precision was <2.0% for both analytes, confirming the
method is precise (Table 2).
Conclusion
The statistical data have been proven that developed HPLC procedure for simultaneous estimation of
ibuprofen and famotidine was found to be accurate,
precise, and sensitive. Therefore the proposed method can be applied for routine quality control analysis.
Table 1. Statistical data for accuracy
Statistical data
% Recovery
SD*
% RSD

ibuprofen
99.75
1.451
1.45

famotidine
99.24
1.852
1.87

*Average value of three determinations, RSD is relative

standard deviation
Table 2. Precision of the method
ibuprofen
Amount
Amount
claimed
found (mg/
(mg/tablet)
tablet)
99.75
99.52
100.1
400.0
99.63
100.2
100.1
Mean*
99.88
Sd
0.286
%RSD
0.29
*Mean of three determinations

famotidine
Amount
Amount
claimed
found (mg/
(mg/tablet)
tablet)
13.01
13.56
13.49
13.30
13.21
13.25
13.08
Mean
13.27
Sd
0.219
%RSD
1.65

PHARMACIA, vol. 61, No. 2/2014

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L. Peikova, M. Georgieva, B. Tsvetkova

PHARMACIA, vol. 61, No. 2/2014

Corresponding author
L. Peikova
Mobile: +359 (0)898 454851;
Tel: +3599236538 ; Fax: +3599879874;
E-mail address: lily_peikova@yahoo.com

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