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A gravimetric method for the determination of diclofenac in pharmaceutical preparations was developed. Diclofenac is precipitated from aqueous solution with copper(II) acetate in pH 5.3 (acetic acid/acetate buffer). Sample aliquots had approximately the same quantity of the drug content in tablets (50 mg) or in ampules (75 mg). The observed standard deviation was about [ or -] 2 mg; therefore, the relative standard deviation (RSD) was approximately 4% for tablet and 3% for ampule preparations. The results were compared with those obtained with the liquid chromatography method recommended in the United States Pharmacopoeia using the statistical Student’s Mest. Complete agreement was observed. It is possible to obtain more precise results using higher aliquots, for example 200 mg, in which case the RSD falls to 1%. This gravimetric method, contrary to what is expected for this kind of procedure, is relatively fast and simple to perform. The main advantage is the absolute character of the gravimetric analysis.

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Diclofenac, 2-[(2,6-dichlorophenyl)amino] benzene acetate (Figure 1), is a synthetic nonsteroidal compound that is usually found as the sodium or potassium salt (1). It is used as an anti-inflammatory and antirheumatic. It was introduced for the treatment of inflammations in 1975.
Since that year, analytical procedures appeared in the literature for its determination in biological materials (2). However, only since 1987 has more attention been devoted to analytical procedures for pharmaceutical preparations. Several techniques have been described, for example, liquid chromatography (LC; 3-8), fluorometry (9-12), potentiometry (12-14), capillary electrophoresis (15, 16), thermal analysis (17), atomic absorption spectrometry (AAS; 18), flow-injection methods (19-23), ultraviolet (UV) spectrophotometry (24, 25), and visible (Vis) spectrophotometry (26-37). All of these methods need calibration plots to be used. As far as we know, gravimetric methods for the determination of diclofenac in pharmaceutical preparations have not yet been developed. Gravimetric methods are usually very slow but present the interesting advantage that they do not need a calibration plot.
The aim of the present work was to develop a reliable, simple, and relatively fast gravimetric method for the determination of diclofenac in pharmaceutical preparations.
Experimental
Apparatus
(a) Liquid chromatograph.–Waters 600 E (Waters Corp., Milford, MA) with UV-Vis 484 detector and a Microsorb MV C-18, 5 [micro]m, 25 cm x 4.6 mm column were used for analytical comparative purposes.
(b) Balances. Mettler AE200 (Greifensee, Switzerland), d = 0.1 mg.
(c) Centrifuge.–Fanem Model 206 BL (Sao Paulo, Brazil) with a horizontal 8 tube swing-out rotor, speed up to 3500 rpm (58 rps).
(d) Differential scanning calorimeter.–DuPont Model 910 (Wilmington, DE).
(e) Filter.–Figure 2 shows a homemade filtering glass piece used for the filtration in the centrifuge.
Reagents
All reagents were of analytical grade.
(a) Diclofenac salts.–Pharmaceutical 99.9% certified products supplied by a pharmaceutical laboratory (Nortec Quimica, Duque de Caxias, Brazil). The products were titrated potentiometrically with perchloric acid in glacial acetic acid solution to confirm diclofenac content (36).
(b) Water.–Distilled in a glass apparatus and then deionized in a Milli Q Plus device.
(c) Copper(II) acetate solution.–50 mg/mL (0.25 M), prepared by dissolving Cu([CH.sub.3]C[O.sub.2])2-[H.sub.2]O (molar mass = 199.65) in water with addition of 0.1 M acetic acid in (9 1, v/v) proportion.
(d) Acetic acid.–O.1 M; 6.0 g glacial acetic acid was dissolved in 1.0 L water.
(e) Buffer solution.–To obtain the pH = 5.3 buffer solution, adequate volumes of 2.0 M sodium acetate and 2.0 M acetic acid solutions were mixed.
Sample Treatment
Groups of 40 tablets of each of the different pharmaceutical preparations containing diclofenac were triturated and homogenized with a mortar and pestle. This material was used to develop the method. In the case of liquid samples, the contents of 5 ampules were mixed, and adequate samples were taken from the total volume.
[FIGURE 1 OMITTED]
Portions corresponding to the mass of 1 tablet of the pharmaceutical preparation (nominal value 50 mg) were weighed and dissolved in 7 mL hot water (85[degrees]C) using the following technique. Initially, each aliquot was treated with 3 mL hot water for 1 min. The solution was then carefully filtered (quantitative rapid filter paper) directly in a small beaker, avoiding the transfer of the solid residue. This residue was treated again with 3 mL hot water as before. The filter paper was finally washed with 1 mL hot water. Therefore, the total volume in the beaker was about 7 mL. To this beaker, 4.0 mL of the 50 mg/mL copper(II) acetate solution and 4.0 mL of the acetic acid/sodium acetate buffer (pH = 5.3) were added. The content was gently mixed for 1 min with a thin glass rod (about 1 mm diameter). This final solution containing a light green precipitate was filtered through a sintered glass filter (G3) in the centrifuge (Figure 2). Initially for 30 s, the rotation of the centrifuge was adjusted at 16 rps to promote the deposition of the larger particles, with the intention of decreasing the porosity of the filter, and avoiding the passage of the smaller particles. Then, the rotation was increased to 58 rps for 1 min. As the volume of the filtering piece was relatively small, it was necessary to repeat the process until the filtration of the complex was complete. At the end, the beaker was washed with ca 2 mL of water that was also filtered to transfer possible remaining copper(II)-diclofenac precipitate. A final washing of the precipitate in the filter was done with ca 2 mL cold water to remove soluble compounds.