Simultaneous determination of ibuprofen and paracetamol using derivatives of the ratio spectra method

2.1 Apparatus

A Shimadzu 1601 double beam UV–Vis spectrophotometer with a fixed slit width (2 nm) connected to an IBM compatible computer and a HP 600 inkjet printer was used. The bundled software was UV PC personal spectroscopy version 3.91 (Shimadzu).

2.2 Materials and reagents

Pharmaceutical grade of ibuprofen and paracetamol were kindly supplied by Rameda (6 October City, Egypt), analytical grade methanol (Riedel-dehaen) was used throughout these experiments. The commercial Cetofen tablets used containing 200 mg IB and 325 mg PA per tablet was manufactured by Sigma Company.

2.3 Standard solutions

Stock solutions of 1 mg/ml of IB and PA were prepared by dissolving 100 mg of each drug in 100 ml methanol. The standard solutions were prepared by dilution of the stock solutions with the same solvent to reach concentration range 2–32 and 2–24 μg/ml for IB and PA.

2.4 Procedure

2.5 Sample preparation

Twenty tablets were weighed and finely powdered in a mortar, an amount of the tablets powder equivalent to 100 mg IB and 162.5 mg PA was dissolved in about 60 ml methanol and filtered in a 100 ml measuring flask, the residue was washed three times with 10 ml methanol, then completed to the mark with the same solvent, appropriate solutions were prepared by taking suitable aliquots of this solution.

3.1 Derivative ratio spectra method

The advantages of the derivative ratio spectra method over the zero-crossing derivative method, is the possibility of performing measurements in correspondence of peaks, hence, a potentially greater sensitivity and accuracy, also in the derivative ratio method the easy measurement on the separate peaks and no need to work only at zero-crossing point as in case of derivative methods. To optimize the simultaneous determination of IB and PA by using ¹DD in case of IB and ²DD in case of PA, it is necessary to test the influence of the variable: divisor standard concentration, Δλ, and smoothing functions. All of these variables were studied. For the determination of IB, the smoothed at Δλ = 2 nm UV spectra of IB standard solutions of increasing concentrations in methanol in its binary mixture with PA were divided by the spectrum of various divisor concentrations smoothed at Δλ = 2 nm, and the first derivative of the spectrum obtained were calculated, the results show that a standard spectrum of 20 μg/ml of PA was considered as suitable divisor for the determination of IB, also the influence of Δλ for obtaining the first derivative of the ratio spectra was tested and Δλ = 4 nm was selected as optimum value. The spectra are represented in Fig. 2. The concentration of IB was proportional to the amplitude at 225.6 nm in the concentration range 2–32 μg/ml. Similarly for determination of PA, the smoothed at Δλ = 2 nm UV spectra of PA standards of increasing concentrations in methanol in its binary mixture with IB were divided by the spectrum of various divisor concentrations smoothed at Δλ = 2 nm and the second derivative of the spectrum obtained were calculated. The results show that a standard spectrum of 14 μg/ml of IB was considered as a suitable divisor for the determination of PA, and the optimum value of Δλ was found equals 8 nm, the obtained spectra are represented in Fig. 3. As seen in the figure there exist two maxima (238.9 and 241.3 nm) and two minima (244.6 and 247.0 nm), we found that measured signals at these wavelengths are proportional to the concentration of the drug in the concentration range 2–24 μg/ml, 238.9 nm was selected for the determination of the synthetic mixtures and commercial tablets due to the low standard deviation and suitable mean recovery. For ¹DD and ²DD methods, the characteristic parameter of regression equations, and detection limit (Miller and Miller, 1993) are given in Table 1. The regression curve was calculated by the least squares method. The correlation coefficients were near unity indicating good linearity.

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Figure 2

First derivative of the ratio method of a, 2; b, 4; c, 6; d, 8; e, 12; f, 16; g, 20 μg/ml solution of ibuprofen when 20 μg/ml solution of paracetamol used as divisor.

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Figure 3

Second derivative of the ratio method of a, 2; b, 4; c, 6; d, 8; e, 10; f, 12; g, 14; h, 16, i, 18; j, 20 μg/ml solution of paracetamol when 14 μg/ml solution of ibuprofen used as divisor.

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In order to demonstrate the validity and applicability of the proposed methods, recovery studied were performed by analyzing synthetic mixtures of IB and PA which represent different composition ratios, the results are summarized in Table 2. Satisfactory recoveries with small standard deviations were obtained which indicated the high repeatability and accuracy of the two proposed methods.

3.2 Analysis of tablets

The proposed method was applied to the determination of IB and PA in commercial Cetofen tablets (200 mg IB and 325 mg PA per tablet). Satisfactory results were obtained for both drugs and were in a good agreement with the label claims and indicate that there is no interference from the excipients used in the formulation of the tablets (Table 3).

The results obtained by using the proposed method were statistically compared with the reported least squares method (Basu et al., 1998) using student t- and F-test (at 95% confidence level) (Miller and Miller, 1993). The results (Table 4) show that the calculated t- and F-values were less than the theoretical ones, indicating no significant difference between the proposed and reported methods.