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Journal of Chromatographic Science, Vol. 48, November/December 2010

TLC Chromatographic–Densitometric Assay

of Ibuprofen and Its Impurities

Małgorzata Starek* and Jan Krzek

Department of Inorganic and Analytical Chemistry, Jagiellonian University, Collegium Medium, 9 Medyczna Str., 30-688 Cracow, Poland

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Abstract raphy (GC) (4,9), capillary isotachophoresis (10), spectrofluo-
rometry (11), and potentiometric titration in non-aqueous
A simple and sensitive thin-layer chromatographic media (12). A high-performance thin layer chromatography
(TLC)–densitometric method for the quantitative estimation of (HPTLC) method with n-hexane–ethyl acetate–anhydrous acetic
S(+)-2-[4-isobutylphenyl]propionic acid (ibuprofen) and its acid as mobile phase, for quantitation of ibuprofen from human
impurities in pharmaceutical preparations has been developed. plasma was described (13). The application of tandem mass spec-
The chromatographic separation was carried out on silica gel 60 trometry to the analysis and identification of paracetamol,
F254 TLC plates using toluene–ethyl acetate–glacial acetic acid ibuprofen, and indomethacin following TLC with silica gel and
(17:13: 1, v/v/v) as the mobile phase. Detection was carried out diol-bonded silica gel HPTLC plates, in biological samples was
densitometrically with a UV detector. The developed method has reported (15). HPLC and TLC (supplemented with UV spectrom-
detection and quantitation limits ranging from 0.13 µg per spot to
etry) methods for simultaneous determination and separation of
0.72 µg per spot. For individual constituents the recovery ranged
from 96.8% to 99.0%. In addition, the stability of ibuprofen
paracetamol, ibuprofen, and diclofenac from commercial formu-
solutions was investigated, including the effect of pH, temperature, lations were presented. They were extracted, isolated, purified,
and recrystallized, and they were characterized by melting point,
λmax and IR (5). TLC with videodensitometry for separation and
and incubation time. The method is rapid, simple, and suitable for
routine quality-control analysis of pharmaceuticals containing
ibuprofen. identification of fenbufen, ibuprofen, ketoprofen, diclofenac
sodium, mefenamic acid and tiaprofenic acid on normal-phase
and reversed-phase plates has been presented (15).
TLC is the most simple and basic analytical procedure and is
Introduction used for the separation of widely applicable compounds. A TLC
method has become useful as a technique due to its advantages
S(+)-2-[4-isobutylphenyl]propionic acid (S(+)-ibuprofen) of reliability in quantitation of analytes at micro or nanogram
belongs to a class of nonsteroidal drugs inhibiting the activity of levels and its cost effectiveness. The major advantage of TLC is
the enzyme cyclooxygenase and has strong analgesic and that several samples can be analyzed using a small quantity of
antipyretic action (1). It is used in the treatment of pain which mobile phase. This reduces the time and cost of analysis.
coexists with inflammation. It is widely used in the treatment of TLC–densitometry also facilitates repeated detection of the com-
pain from rheumatic illnesses, myalgias, post-traumatic neural- ponents of the chromatogram with the same and different
gias, migraine headaches, fevers, head colds, and the symptoms parameters. Moreover, the method enables simultaneous anal-
of influenza. ysis of several compounds. TLC is comparable with other
For studying the quality of medicines with ibuprofen, various methods used for drug analysis, for example HPLC and GC.
pharmacopoeias recommend different analytical methods such Through continuing research of the efficiency of methods for
as spectroscopy (IR and UV) and the thin-layer chromatography the chromatographic determination of non-steroidal anti-
(TLC) on silica gel plates with anhydrous acetic acid–ethyl inflammatory drugs and the significance of the sensitivity and
acetate–hexane (5:24:71, v/v/v) as mobile phase (2,3). For the reliability of TLC in the analysis of pharmaceutical preparations
estimation of drug purity, liquid chromatography (LC) is the rec- (16–18), an attempt was made to develop a novel, simple, rapid,
ommended method. and validated TLC–denitometry method, which considerably
Survey of the literature reveals various methods available for improved the efficiency for ibuprofen estimation in drugs. The
the determination of ibuprofen. The methods include high-per- present study established the conditions for identification and
formance liquid chromatography (HPLC) (4–8), gas chromatog- quantitation of ibuprofen in presence of its impurities, 2-[4-
isobutyrylphenyl]propionic acid and 2-[4-isobutylphenyl]-propi-
onamide (2,3). In addition, the effect of pH, temperature and
*Author to whom correspondence should be addressed: email mstarek@interia.pl. incubation time on ibuprofen stability was investigated.

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Journal of Chromatographic Science, Vol. 48, November/December 2010

Experimental Sample solutions

Tablets. Ten tablets were finely ground in a mortar; an amount
Apparatus corresponding to 10 mg of ibuprofen was weighed and then 10.0
All designed experiments were carried out with a densitometer mL of methanol was added and shaken for 30 min; the solution
TLC Scanner 3 with Cats 4 software, (Camag, Muttenz, was filtered and used in further analysis (solution A1).
Switzerland). Solutions were applied by sample applicator Granulate. A mass of the five sachets corresponding to 10 mg
Linomat V, (Camag). Silica gel aluminium TLC F254 plates, art. of ibuprofen was weighed and then 10.0 mL of methanol was
No 1.05554 were obtained from E. Merck, Darmstadt, Germany. added and shaken for 30 min; the solution was filtered and used
Chromatograms were developed in a TLC chamber of 18 × 9 × 18 in further analysis (solution A2).
cm in size (Sigma-Aldrich, St. Louis, MO). 1H NMR analysis were Suspension. The volume of the preparation corresponding to
carried out on a spectrometer NMR Mercury VX 300MHz, 10 mg of ibuprofen was pipeted, and then methanol was added to
(Varian, Palo Alto, CA). 10.0 mL and shaken for 30 min; the solution was used in further
analysis (solution A3).
Reagents and chemicals In the next step, 1.0 mL of solutions A1, A2 or A3 was made up

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Standard substances with methanol in a 10.0 mL flask (solution B).
S(+)-2-[4-isobutylphenyl]propionic acid (S(+)-ibuprofen;
Fluka), 2-[4-isobutyrylphenyl]propionic acid (impurity B) Establishing TLC conditions
Standard solutions were applied on silica gel aluminium TLC
F254 plates, cut from 20 × 20 cm before use. Different volumes of
(STADA) and 2-[4-isobutylphenyl]propionamide (impurity A)
(STADA) were used.
the solutions (from 1 to 50 µL) were applied to the plates in trip-
Reagents licate, as 10 mm bands, 10 mm apart, 10 mm from the lower
Methanol, (Merck), toluene, ethyl acetate, (POCH, Gliwice, edge of the plate by means of a Linomat V automatic spray-on
Poland), and glacial acetic acid (Odcz. Sp.z o.o., Poland) were sample applicator equipped with a 100 µL syringe. The distance
used. All the reagents were of analytical grade. from the side of the plate to the first band was also 10 mm. The
plates were then developed to different distances (from 8 to 18
Samples cm) with experimentally selected mobile phases in a TLC
The following medicines were analyzed: Ibuprom, tablets con- chamber, previously saturated with the mobile phase vapor for
taining 200 mg of ibuprofen (US Pharmacia Int., Rockville, MD); 15 min at room temperature. For the distance of 13 cm the con-
Ibuprofen, tablets containing 200 mg of ibuprofen (Polfa stituents were well separated in ~40 min (Figure 1). After devel-
Pabianice, Pabianice, Poland); Nurofen, tablets containing 200 opment the TLC plates were dried in a current of air.
mg of ibuprofen (Boots Healthcare Int., Nottingham, UK); Densitometric scanning to locate spots on the chro-
Nurofen, granulate containing 200 mg of ibuprofen per 2.1 g of matograms was performed with a TLC Scanner 3, equipped with
granulate (Boots Healthcare Int.); Ibufen, suspension containing the deuterium light source, in linear reflectance/absorbance
mode, controlled by CATS 4 Software resident in the system. The
slit dimensions were 8 × 0.45 mm, the scanning speed 20 mm/s
100 mg of ibuprofen per 5 mL of suspension (Terpol, Warszwa,
Poland).
and data resolution 100 µm per step. For individual constituents,
Standard and sample solutions the retardation factors Rf were derived from the obtained densi-
Standard solutions tograms. Analysis of UV absorption spectra, registered directly
from chromatograms, recorded in the wavelength range of
200–400 nm, showed that maximum absorbance occurred at λ =
Solutions of concentration 0.1 mg/mL of ibuprofen, impurity
A, and impurity B in methanol were prepared.

Figure 1. Densitogram of standard substances: 2-(4-isobutylphenyl)-propi- Figure 2. Absorption spectra of ibuprofen (I), 2-(4-isobutylphenyl)-propi-
onamide (1, impurity A), 2-(4-isobutyrylphenyl)propionic acid (2, impurity B) onamide (impurity A), 2-(4-isobutyrylphenyl)propionic acid (impurity B) and
and ibuprofen (3), obtained directly from chromatogram. degradation product (impurity X), obtained directly from the TLC plate.

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Journal of Chromatographic Science, Vol. 48, November/December 2010

222 nm for ibuprofen and impurity A and λ = 252 nm for impu- standard and sample solutions. Three measurements were made
rity B (Figure 2). The amount of the chromatographed com- for each determination. The mean values were taken as a final
pounds was determined from the intensity of diffusely reflected result. Received results with the statistical estimation were
light. assembled in Table I. On the received densitograms there were
no other peaks, beside the peaks originating from the active sub-
Quantitative analysis stance.
The standard solutions at volume of 8 µL for ibuprofen, impu-
rity A, and impurity B as well as 4 µL for sample solutions (solu- Validation of the method
tions B) for determining active substance and 20 µL of sample To confirm reliability of the results the method was validated
solutions (solutions A) for determining impurities, were applied (19). The results are presented in Table II.
with the applicator to 9 × 13 cm plates. Chromatograms were The specificity of the method was determined by comparing
developed to a distance of 13 cm with toluene–ethyl the chromatograms obtained from the model solutions con-
acetate–glacial acetic acid (17:13:1, v/v/v) as mobile phase. After taining ibuprofen with those obtained from blank model solu-
development the plates were dried at room temperature. The tions and analyzing them for peaks interfering with the detection

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densitometric measurements were made at 222 nm and 252 nm. of active substance. For methanol extracted solutions used for
If no additional peak of Rf = 0.63 is registered on chromatograms determination purposes, no additional spots were found, except
at λ = 252 nm, analysis may be carried out at λ = 222 nm. for ibuprofen.
The concentration of constituents in preparation under exam- The linearity was checked on six solutions of various concen-
ination were computed by comparing the peak areas for relevant trations varying from 0.50 to 1.75 µg per spot for ibuprofen, from
6.00 to 16.00 µg per spot for impurity A and from 0.40 to 1.39 µg
Table I. Ibuprofen Determination in Preparations* per spot for impurity B. The results were analyzed by employing
the linear regression method.
Preparation Determined amount of ibuprofen Limits of detection (LOD) and quantitation (LOQ) were deter-
(declared amount of ibuprofen) Statistical analysis (n = 6)
mined on the basic of the standard deviation of the response and
slope of the straight lines, obtained from the equations: LOD =
3.3 × SD / a and LOQ = 10 × SD / a, where SD is the standard devi-
Ibuprofen xm = 207.55 mg
(200 mg in tablet) S = 4.04 Sx m = 1.65
µ = 207.55 ± 4.24 RSD = 1.95 ation of the response and a is the slope of the calibration curve.
Nurofen xm = 207.32 mg The precision of the method was expressed as a consistence
(200 mg in tablet) S = 3.65 Sx m = 1.49 degree between the results of analyses carried out repeatedly.
µ = 207.32 ± 3.83 RSD = 1.76 The tests were conducted for a model mixture solution con-
Ibuprom xm = 201.28 mg taining ibuprofen, impurity A, and impurity B. The precision was
(200 mg in tablet) S = 4.52 Sx m = 1.85 estimated using peak areas of individual constituents and was
µ = 201.28 ± 4.76 RSD = 2.25 evaluated by the standard deviation and relative standard devia-
Ibufen xm = 99.35 mg tion. Intermediate precision was determined by analyzing the
(100 mg in 5 mL of suspension) S = 2.13 Sx m = 0.87 same solutions on three different days over a period of one week.
µ = 99.35 ± 2.24 RSD = 2.14 Recovery was calculated by comparing the mean analytical
Nurofen xm = 201.50 mg results for the drug solutions with the theoretical value of the
(200 mg in 2.1 g of granulate) S = 3.71 Sx m = 1.51 added weight of appropriate substance. The accuracy of the
µ = 201.50 ± 3.88 RSD = 1.84 method was expressed in percentage of the recovery of added
* Arithmetic mean (xm); standard deviation (S); standard deviation of arithmetic mean analyte within the range from 80% to 120% of relevant sub-
(Sx m); confidence interval at 95% probability (µ); relative standard deviation percent stances compared with the preparations under examination. The
(RSD).
recovery (R[%]) was computed from the formula: R [%] = [(A –
Ai) / Ai] × 100%, where: A is the peak area [mm2]
Table II. Validation Parameters of the Proposed TLC Method* obtained for the sample solution after adding a spec-
ified amount of analyte and Ai is the peak area [mm2]
Parameter Ibuprofen Impurity A Impurity B
obtained before the analyte was added.
λ (nm) 222 222 222 252
Rf 0.72 0.54 0.63 0.63 Examination of ibuprofen stability in solutions
Linearity P = 19.177 × c – 402.7 P = 6.247 × c + 507.8 P = 1284.0 × c + 2401.8 P = 12.649 × c + 433.8 An effect of pH, temperature, and incubation time
R = 0.99286 R = 0.99626 R = 0.99548 R = 0.99121 on stability of ibuprofen in solutions was investi-
LOD (µg/spot) 0.24 0.13 0.15 0.17 gated. For this purpose, weighed amounts of approx-
LOQ (µg/spot) 0.72 0.40 0.46 0.51
Precision RSD = 1.30 RSD = 1.62 RSD = 1.44 RSD = 2.06
imately 10 mg of ibuprofen were dissolved in 5 mL of
Intermediate RSD = 1.85 RSD = 2.04 RSD = 1.98 RSD = 2.33 hydrochloric acid or sodium hydroxide solution at a
precision concentration ranging from 0.1 to 1.0 mol/L. The
Accuracy xm = 99.03% xm = 96.75% xm = 98.02% xm = 97.56% solutions were incubated at temperatures of 22, 37,
RSD = 1.32 RSD = 2.62 RSD = 2.03 RSD = 2.45 and 70°C, while taking analyte samples at specified
* Peak area (P); concentration (c); correlation coefficient (R); arithmetic mean (xm). time intervals (from 7, 13–22 days). The samples
were diluted with methanol (1:1, v/v) for quantita-

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Journal of Chromatographic Science, Vol. 48, November/December 2010

tive analysis. Internal normalization method to determine the good separation, and at the same time gave well developed peaks,
percentage constituent concentration was used. The results important for good densitometric analysis. In addition to the
obtained were used for kinetic and thermodynamic evaluation of values of retardation factors (Rf = 0.74 for ibuprofen, Rf = 0.54 for
the ibuprofen decomposition process, by determining the reac- 2-[4-isobutylphenyl]propionamide [impurity A] and Rf = 0.63 for
tion rate constants k, half-life t0.5 and the time t0.1 in which the 2-[4-isobutyrylphenyl]propionic acid [impurity B]) for individual
concentration of ibuprofen is reduced by 10%, as well as activa- constituents well developed and repeatable absorption spectra
tion energy Ea, according to the kinetics of a first order reaction were recorded directly from chromatograms to aid in qualitative
(20). The results are presented in Table III. analysis (Figures 1,2).
The method presented above fulfills the principal require-
ments of good laboratory practices, both in the terms of quanti-
tative analysis and determination of active substances and
Results and Discussion impurities. It is important that the method is characterized by
good precision (RSD = 1.30–2.06%), high sensitivity (LOD from
A chromatographic–densitometric method was developed to 0.13–0.72 µg per spot) and constituent detection, ranges of lin-

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simultaneously separate and determine the active substance of earity and satisfactory recovery values varying from 96.8% to
ibuprofen and its impurities. The conditions for separation of 99.0%. The results of determination of ibuprofen in the pharma-
ibuprofen and analyzed impurities and the method for chro- ceutical products confirmed accuracy and good precision of the
matographic identification were established by using appro- method. The obtained average contents of the active constituent
priate standard solutions. are close to the declared content (Table I).
The application of the mobile phase consisting of: In the next part of the work the effect of pH in aqueous solu-
toluene–ethyl acetate–glacial acetic acid (17:13:1, v/v/v) provided tions on ibuprofen decomposition was analyzed. In addition to
the ibuprofen peak, some additional peaks were observed on
Table III. Kinetic and Thermodynamic Parameters Describing chromatograms depending on test conditions. In acidic environ-
Degradation Process of Ibuprofen in Acidic Solutions* ment, ibuprofen decomposes into two products (Rf (1) = 0.54 and
Rf (2) = 0.90), while no additional peaks besides the peaks
HCl conc. Temp. k (h–1) t0.1 (h) t0.5 (h) originating from ibuprofen were observed in basic solutions
(Figure 3).
1 mol/L 22°C 5.04 × 10–4 209 1375 To identify the degradation products (impurity A and impurity
37°C 8.64 × 10–4 122 802 X), Rf values and UV spectra were recorded directly from chro-
70°C 2.53 × 10–3 42 274 matograms, and 1H NMR spectra were registered. Ibuprofen
0.5 mol/L 22°C 2.03 × 10–4 457 3414 solution after hydrolysis in 1 mol/L HCl was separated on a chro-
37°C 4.33 × 10–4 243 1600
matotron plate and after fraction separating, the solvent was
70°C 1.46 × 10–3 72 475
Ea (1 mol/L) = 2.87 × 104
evaporated and the products were identified with 1H NMR
Ea (0.5 mol/L) = 3.25 × 104
spectra comparative analysis. Because of very small amounts of
degradation products, 1H NMR analysis did not bring any reliable
* Stability constant [k (h–1)]; time, concentration will decrease about 10% [t0,1 (h)]; time, results for the structure determination.
concentration will decrease about 50% [t0,5 (h)]; energy of activation [Ea (J/mol × K)].
On the ground of Rf values and absorption spectra, one can
suppose that the spot of the ibuprofen’s degradation product (Rf
= 0.54) originated from 2-[4-isobutylphenyl]propionamide
(impurity A). This spot originated from acidic hydrolysis of the
ibuprofen and corresponded to the appropriate spot from the ref-

Figure 3. Densitogram obtained after ibuprofen decomposition in acidic envi- Figure 4. Concentration changes of ibuprofen (% I) in acidic solutions. Samples
ronment (1 = impurity A; 2 = ibuprofen; 3 = impurity X). were incubated for 1 h at 70°C.

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Journal of Chromatographic Science, Vol. 48, November/December 2010

phenyl]propionamide was developed. This TLC-densitometric

method can be regarded as an alternative to the more widely
used HPLC, because sample preparation is simpler and there is a
possibility of multi-sample analysis which reduces analysis cost
and time for individual samples. The proposed method is charac-
terized by high specificity, and also accurate and precise enough
to be successfully adopted as an alternative to the existing
methods for evaluation of drugs in pharmaceutical preparations
and quality control.

References
Figure 5. The relationship between concentration of ibuprofen (log % I) and
1. J.K. Podlewski and A. Chwalibogowska–Podlewska. Leki Współczesnej Terapii

Downloaded from https://academic.oup.com/chromsci/article/48/10/825/410535 by guest on 09 January 2024

incubation time. The studies were carried out in 1 mol/L HCl solution at 70°C. (Medicines of Modern Therapy). Fundacja Buchnera Ed., Warszawa, Poland,
1999.
2. European Pharmacopoeia. 5th ed., Council of Europe, Strasbourg, France, 2002.
erence substance. Unfortunately, it has not been possible to iden- 3. British Pharmacopoeia. Her Majesty’s Stat. Office, London, United Kingdom,
tify the spot with Rf = 0.90 (impurity X) yet. 2002.
4. R.A. Sodhi, J.L. Chawla, and R.T. Sane. Simultaneous determination of parac-
The concentrations of degradation products vary with etamol, ibuprofen and chlorzoxazone by HPLC, HPTLC and GC methods. Indian
hydrochloric acid concentration, temperature, and incubation Drugs. 33: 280–285 (1996).
5. R. Bhurshan, D. Gupta and A. Makherjee. Liquid chromatographic analysis of
time. Any effects of HCl concentration, temperature, and heating certain commercial formulations for non-opioid analgesics. Biomed.
time on ibuprofen decomposition were examined. Chromatogr. 21: 1284–1290 (2007).
6. A.A. Overbeke, W. Baeyens, W. Van Den Bossche, and C. Dewaele. Separation
Degradation of ibuprofen depends on the acid concentration of 2-arylpropionic acids on a cellulose based chiral stationary phase by
(Figure 4). In acidic solutions at concentration of 0.2 mol/L and RP–HPLC. J. Pharm. Biomed. Anal. 12: 901–909 (1994).
7. V.E. Haikala, I.K. Heimonen, and H.J. Vuorela. Determination of ibuprofen in
smaller, incubated at 70°C for 1 h, concentration change of ointments by reverse–phase LC. J. Pharm. Sci. 80: 456–458 (1991).
active substance is less than 10%, contrary to experiments car- 8. J. Sochor, J. Klimes, J. Sedlacek, and M. Zahradnicek. Determination of ibuprofen
in erythrocytes and plasma by HPLC. J. Pharm. Biomed. Anal. 13: 899–903
ried out in 0.5 and 1.0 mol/L solutions. The degradation process (1995).
of ibuprofen depends on the incubation time. During longer 9. I. Rodriguez, J.B. Quintana, J. Carpinteiro, A.M. Carro, R.A. Lorenzo, and R. Cela.
Determination of acidic drugs in sewage water by GC–MS as tert-
incubation time, concentration of degradation products butyldimethylsilyl derivatives. J. Chromatogr. A 985: 265–274 (2003).
increases and concentration of active substance decreases. The 10. J. Sadecka, M. Cakrt, A. Hercegova, J. Polonsky, and I. Skacani. Determination of
relationship between log concentration of ibuprofen and time ibuprofen and naproxen in tablets. J. Pharm. Biomed. Anal. 25: 881–891 (2001).
11. P.C. Damiani, M. Bearzotti, and M.A. Cabezon. Spectrofluorometric determina-
indicates that the degradation process of ibuprofen is consistent tion of ibuprofen in pharmaceutical formulations. J. Pharm. Biomed. Anal. 25:
with kinetics for first-order reactions (Figure 5). 679–683 (2001).
12. O. Cakirer, E. Kilic, O. Atakol, and A. Kenar. Non-aqueous titrimetric assay of the
Temperature also influences on the stability of ibuprofen in selected anti-inflammatory agents using tetra-n-butylammonium hydroxide as
acidic solutions. A temperature rise up to 70°C led to a decom- titrant. J. Pharm. Biomed. Anal. 20: 19–26 (1999).
13. T.K. Save, D. V. Parmar, and P.V. Devarajan. High-performance thin-layer chro-
position of ibuprofen to ~65% in a week. Reaction rate constants matographic determination of ibuprofen in plasma. J. Chromatogr. B. 690:
for the degradation of ibuprofen increase with the increasing 315–319 (1997).
14. W. Morden and I.D. Wilson. The detection and characterization of analgesics and
temperature and concentration of hydrochloric acid (Table III). anti-inflammatory drugs on high performance thin-layer chromatography plates
Stability of ibuprofen described by kinetic parameters t0.1 and t0.5 using tandem mass spectrometry: Application to drugs and metabolites in
urine. Rapid Commun. Mass Spectrom. 10: 1951–1955 (1996).
is twice smaller in 1 mol/L hydrochloric acid than in 0.5 mol/L. 15. H. Hopkała and A. Pomykalski. TLC analysis of non-steroidal anti-inflammatory
Relatively high increase of the reaction rate constant k with the drugs and videodensitometric determination of fenbufen in tablets. J. Planar
Chromatogr.–Mod. TLC. 17: 383–387 (2004).
temperature increasing corresponds to the obtained energy of 16. J. Krzek and M. Starek. Densitometric determination of active constituents and
activation Ea, and proves lower stability of ibuprofen in more impurities in complex analgesic and antipyretic pharmaceuticals. J. Planar
Chromatogr.–Mod. TLC. 12: 356–360 (1999).
acidic solutions. It should be pointed out that under described 17. J. Krzek and M. Starek. Simultaneous densitometric determination of
conditions two degradation products appear on chromatograms indomethacin and its degradation products, 4-chlorobenzoic acid and 5-
(Rf = 0.54 and Rf = 0.90) together with main peak of active sub- methoxy-2-methyl-3-indoleacetic acid, in pharmaceutical preparations. J. AOAC
Int. 84: 1703–1707 (2001).
stance (Rf = 0.74). 18. J. Krzek and M. Starek. Densitometric determination of diclofenac, 1-(2,6-
dichlorophenyl)indolin-2-one and indolin-2-one in pharmaceutical preparations
and model solutions. J. Pharm. Biomed. Anal. 28: 227–243 (2002).
19. ICH Steering Committee, Validation of Analytical Procedures (Q2), 2005.
20. E. Pawełczyk and T. Hermann. Podstawy trwałoci leków. PZWL, Warszawa,
Conclusions Poland, 1982.

An easy and sensitive TLC chromatographic–densitometric

method for simultaneous determination of ibuprofen and impu- Manuscript recieved July 18, 2008;
rities, 2-[4-isobutyrylphenyl]propionic acid and 2-[4-isobutyl- revision recieved June 5, 2009.

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