ЖУРНАЛ АНАЛИТИЧЕСКОЙ ХИМИИ, 2015, том 70, № 1, с. 48-52


УДК 543


© 2015 Sevilay Camalan Türk, Eda §atana, Hasan Basan1, Nilgün Günden Göger

Gazi University, Faculty of Pharmacy, Department of Analytical Chemistry 06330, Etiler, Ankara, Turkey 1E-mail: basan@gazi.edu.tr Received 20.06.2012; in final form 22.05.2014

A flow-injection 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 spectrophotometer 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 p.L and 100, respectively. The analytical signal of ibuprofen was linear in the concentration range of 400—1200 p.g/mL. The detection limit and limit of quantification were determined as 27 and 91 ^g/mL, respectively. Results for the determination of ibuprofen in tablets, 600 ± 2 mg/tablet (mean ± SD), were in good agreement with the labeled quantities, 600 mg/tablet. A relatively high recovery value, 100.4 ± 0.6%, proves the accuracy of the proposed method. The spectrophotometric method and reference HPLC method were shown to be comparable when Student's t-test 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 developed. Recovery values for the determination of ibuprofen and paraben were 102.4 ± 1.1% and 100.2 ± 2.3%, respectively.

Keywords: ibuprofen, flow-injection analysis, UV-VIS derivative spectroscopy, HPLC, paraben, pediatric syrups.

DOI: 10.7868/S0044450215010168

Ibuprofen, a-methyl-4-(2-methylpropyl)benzene-acetic acid, is a derivative of phenyl propionic acid and is used as a nonsteroidal anti-inflammatory agent. Several methods have been described for ibuprofen determination in pharmaceutical formulations including chromatography [1—3], UV spectrophotometry [4—6], colorimetry [7, 8], electrochemical methods [9, 10], NMR [11, 12], FT—IR [13] and capillary zone electrophoresis [14]. Nowadays, flow-injection 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-ß-cyclodextrin.

In this study, a simple, rapid and sensitive flow-injection UV (FI—UV), spectrophotometric method was developed for the determination of ibuprofen in tablets. FI analysis is widely used in routine analysis of pharmaceuticals and also, to the best of our knowledge, there is no study in literature describing a FI—UV spectrophotometric method for the determination of ibuprofen in tablets without using any pretreatment procedure. In addition, it was thought that the proposed method

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 ^-hydroxybenzoic acid, known as hydroxybenzoates or parabens, are common antimicrobial preservatives added to pharmaceutical formulations. For this reason, quantitative determination of preservatives, especially in syrups, is an important part of quality control. Although there are some studies describing HPLC methods for the determination of preservatives in syrups [16, 17], they are time-consuming and high-cost compared to derivative UV spectrophotometric methods. Since ibuprofen and paraben which are present together in syrups interfere with each other, simultaneous determination of ibuprofen is not possible in the presence of paraben. In order to solve

this spectral overlap problem, a fourth order derivative UV spectrophotometry 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 spectrophotometry method. Throughout these two studies, determinations were performed without using any pretreatment procedure.


Apparatus. Spectrophotometry analysis was performed using Shimadzu UV-160A double-beam UV-VIS spectrophotometer. The flow-injection method was achieved by using a flow cell located in the UV spectrophotometer (10 mm quartz cell with 0.3 mL internal volume), and Gilson Minipuls 3 four channel peristaltic pump with Tygon, Pharm Med pink-white tubing. Flow rate and loop volume were 15 mL/min and 193 ^L, respectively; 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 UV-VIS detector set to 264 nm. A HP ODS hypersil column (10 cm x 3.9 mm i.d., 5 ^m particle size) and a HP 3396 series II integrator were used. Typical operating conditions include flow rate (1.5 mL/min), operating temperature (room temperature) and injection volume (20 ^L).

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 ibuprofen in the range of400—1200 ^g/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 paraben, 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 ^g/mL. The mobile phase used in HPLC was o-phosphoric acid-water—methanol (4 : 246 : 750, v/v/v) and detector was set to 264 nm.

Determination of ibuprofen in tablets (flow-injection method). The average mass of 10 tablets was determined and then powdered. An amount of powder equivalent to 20 mg ibuprofen was weighed and transferred 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 filtered. The absorbance values of the solutions were obtained at 265 nm using 0.1 M NaOH as a carrier solution. The ibuprofen content of tablets was calculated by referring to the calibration curve.

Table1. Results for the determination and profen using FI method recovery of ibu-

Amount labeled, mg/tablet 600.0

Found, mg/tablet 600 ± 2

Added, mg 400.0

Recovery (mean ± SD), % (n = 5) 100.4 ± 0.7

Determination of ibuprofen and paraben in syrups (derivative spectrophotometry methods). The syrup volume corresponding to 5 mg of ibuprofen was placed in a 50.0 mL volumetric flask, diluted to the mark with methanol and filtered. Fourth-order derivative absorbance values were measured at 266.8 nm (n = 9). The ibuprofen content in pediatric syrups was calculated using the calibration curve drawn using standard solutions of ibuprofen ranging from 40 to 360 ^g/mL.

For the determination of paraben in pediatric syrups, syrup volume corresponding to 5.0 mg of ibuprofen was placed into a 50.0 mL volumetric flask and diluted to the mark with methanol. After filtration, firstorder derivative absorbance values were obtained at 271 nm (n = 1). By referring to the calibration curve ranging from 8.0 to 16.0 ^g/mL, paraben content in pediatric syrups was determined.


In the first part of this study, quantitative determination 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.

Flow-injection UV spectrophotometric method. Optimization studies. Several parameters, which were taken into consideration in the determination of ibuprofen, were carefully examined and optimum working conditions were determined. For that purpose, 56, 120, 138, 193, and 250 ^L loop volumes were tested. A larger loop volume, i.e., a higher sample concentration, lead to more sensitive determination since small loop volumes resulted in low absorbance values and wide peaks. However, a longer analysis time was needed for each determination. Thus, 193 ^L 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 optimum 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.

4 XyPHAtf AHAtfHTH^ECKOH XHMHH tom 70 № 1 2015



Table 2. Statistical comparison of the proposed FI and reference HPLC method

Labeled, mg Found*, mean ± SD, mg

FI method HPLC method

600 600 ± 2 595.2 ± 2.3

Determination of ibuprofen in tablets. At 265 nm, a linear relationship was observed between the absor-bance values and concent

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