SPECTOPHOTOMETRIC DETERMINATION OF PARACETAMOLE VIA OXIDATIVE COUPLING WITH PHENYLEPHRINE YDROCHLORIDE IN PHARMACEUTICAL PREPARATIONS

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1 SPECTOPHOTOMETRIC DETERMINATION OF PARACETAMOLE VIA OXIDATIVE COUPLING WITH PHENYLEPHRINE YDROCHLORIDE IN PHARMACEUTICAL PREPARATIONS FIRAS MUHSEN AL-ESAWATI * and RAEED MEGEED QADIR ** * Dept. of Chemistry, Faculty of Science, University of Zakho, Kurdistan Region-Iraq ** Dept. of Chemistry, Faculty of Science, University of Duhok, Kurdistan Region-Iraq (Received: June 3, 2010; Accepted for publication: February 2, 2011) ABSTRACT A new, simple, rapid and sensitive spectrophotometric was described in the present study for the indirect determination of paracetamol. The is based on the oxidative coupling reaction of paracetamol ( after acidic hydrolysis to form p-aminophenol) with phenylephrine hydrochloride using atmospheric oxygen as an oxidant in alkaline medium to form a water soluble, stable indophenol dye and has a maximum absorption at 640 nm. Beer s law is obeyed in a concentration range of µg. ml -1 of paracetamol with a molar absorptivity of 7664 L.mol -1.cm -1, the accuracy is 98.86% and the relative standard deviation was less than 1.88% depending on the concentration levels. The proposed has been applied successfully for the determination of paracetamol in some pharmaceutical preparations. KEYWORDRS: Spectrophotometric, Oxidative Coupling,. P INTRODUCTION aracetamol(n-acetyl-p-aminophenol; PCT) is a common analgesic and antipyretic drug that is used for the relief of fever, headaches and other minor aches and pains (1). Various s have been described for determination of paracetamol included chromatographic (2-8), electrochemical (9-13) and (14-18) Spectrophotometric techniques. Ratio Spectra First-Order Derivative UV Spectrophotometry (19), and Artificial Neural Networks (ANN) (20), also has been employed for the spectrophotometric determination of this drug. In this paper we describe a simple and accurate for rapid indirect spectrophotometric determination of paracetamol in pharmaceutical preparations. The is based on the reaction of the hydrolysis protect of PCT to p-aminophenol (abbreviated as PAP) with phenylephrine hydrochloride in alkaline medium. EXPERIMENTAL 1. Apparatus Shimadzu model (UV-160A) double beam UV_VIS spectrometer with 1.0 cm matches silica cells was used to carry out all spectral measurements. A electo. mag model (M 96K) water bath, HANNA model (ph211) microprocessor phmeter and model (HF-400) sensitive balance were used. 2. Reagents All chemicals used were of analytical reagent grade standard. PCT was supplied by S.D.I. (Iraq), PE by S.D.I. (Iraq), Sodium hydroxide by BDH, Hydrochloric acid by Fluka. - A stock solution of PCT (1000 µg.ml -1 ) was prepared by dissolving 0.25gm of pure PCT in 10 ml of ethanol and diluted to 250 ml with distilled water. 150ml of stock solution of PCT was mixed with 25ml of hydrochloric acid (11.8M), an acidic hydrolysis of mixture was made by rflexation the mixture for one hour. The mixture cooled and diluted to 250ml with distilled water to obtain a solution of (600 µg ml -1 ) of p-aminophenol (PAP). A diluting concentration of solution were prepared from the last solution after equivalent the ph of volume of using concentration before the dilution to 7 by sodium carbonate (20%) and then diluted to volume we need. - Working solution of PE (0.1M) was prepared by dissolving gm in 250ml distilled water. - Sodium hydroxide solution (1.0M) was prepared by dissolving 10gm in 250ml distilled water. 3. Procedure for indirect determination of 52

2 Into a series of 25 ml calibrated flask, increasing volumes of (0.5-6 ml) of PCT (as PAP) working solution (25 and 100 µg ml -1 ) were transferred to cover the range of the calibration curve and 7.0 ml of 0.1 M of PE followed by 1.0 ml of 1.0 M of sodium hydroxide, the solution was diluted to the mark with distilled water and allow the reaction mixture to stand for 10 min. The absorbance was measured at 640 nm against reagent blank, prepared in the same way but containing no PCT. The color of the dye solution was stable more than 12 hrs. 4. Procedure for Pharmaceuticals Ten (10) were weighed and powdered finely. An accurate weight, equivalent to one tablet, was transferred into a 100ml calibrate flask, dissolve as completely as possible in ethanol (10-25ml) and dilute to volume with distilled water. Filter and prepare solution of 1000µg/ml of PCT from later and treat it as the same way as mentioned under the general procedure. RESULTS AND DISCUSSION 1. Absorption Spectra: C The result of this investigation indicated that the reaction between PCT (as PAP) and PE in the alkaline medium yield highly soluble colored condensation product which can be utilized as a suitable assay procedure for PCT. This blue colored product showed a maximum absorption at 640 nm, the blank at this wavelength shows zero absorbance (Fig. 1). Table (1): Effect of concentration of reagent ml, volume of PE (0.1 M) Effect of sodium hydroxide concentration To establish the optimum conditions (stability of the dye resulting from the reaction of the PCT with reagent intensity of the dye formed, minimum blank value and relatively rapid reaction rate), the effect of medium of reaction was studied. Only alkaline medium (1.0M of sodium hydroxide) was found to be optimum. Neutral and acidic medium results in low sensitivity of the color and was not stable. The effect of the amount of sodium hydroxide was also investigated and 1.0 ml was found to be optimal. Table (2): Effect of sodium hydroxide concentration ml, volume of Na ( 1.0 M) Fig,(1): Absorption spectrum of (A) reaction product of PCT (as PAP) 12µg ml -1 with PE vs. blank. (B) blank vs. distilled water. (C) reaction product vs. 2. Study of the optimum reaction conditions The effects of various parameters on the absorption intensity of the dye were studied and the reaction conditions were optimized. 2.1-Effect of reagent concentration Various concentration of PE was added to a fixed concentration of PCT (as PAP), and the results shown that 7.0 ml of 0.1 M of reagent solution was sufficient to develop the color to its full intensity and give the maximum value of absorbance with minimum absorbance of blank Effect of temperature The effect of temperature on the color intensity of the dye was studied. In practice the absorbance was decreased when the color is developed at 0 C or when the calibrated flask is placed in a water bath at C. Therefore, it is recommended to undergo the reaction at room temperature (25 C). 53

3 2.4- Effect of time The color intensity reached maximum after the PCT solution was reacted in development time was selected to be used in the general proceeds with PE and sodium hydroxide for 10 min. Temp. ( C) Table ( 3): Effect of time and temperature / Minutes standing time / Hour standing time Overnight Room temp Accuracy and precision To determine the accuracy and precision of the, PCT (as PAP) was determined at three different concentrations. The results are shown in table.1 indicate that satisfactory precision and accuracy could be attained with the proposed. Table (4): Accuracy and precision of the. taken µg Relative error %* Relative standard deviation%** * Average of three determinations. ** Average of six determinations 3. Calibration curve Under the above optimum conditions, the linear calibration curve (Fig.2) for PCT (as PAP) is obtained which shows that beer's law is obeyed over the concentration range of ( µg ml -1 ) with correlation coefficient of and an intercept of and slope of the molar absorptivity of the colored product was 7664 L.mol -1.cm -1. Fig (2): Calibration curve for indirect determination of PCT. 4. The nature of reaction product The stoichiometry of the reaction between PCT (as PAP) and PE was investigated using the molar ratio (21). The results obtained (Fig.3) shows a 1:1 of the colored product formed between PCT and PE at 640 nm µg/ml (PCT) Mole Ratio of PE/PCT (as PAP) Fig (3): Mole ratio of reaction product of PCT (as PAP)-PE. 54

4 5. Proposed reaction mechanism The acidic hydrolysis of (I) is formed p-aminophenol (II) which readily oxidized by atmospheric oxygen to p- benzoquinonimine, the later couples with phenylephrine hydrochloride (III) in alkaline medium to form a water soluble indophenol dye (IV) which has maximum absorption at 640nm: Table 5: Determination of paracetamol in pharmaceutical preparations Pharmaceutical preparation Label claim mg BP Recovery % Reported Proposed NH CH O Paracetol CH 3 HCl NH 2 Algesic R (I) + NH 2 - H N (II) R Myogesic (III) R= CH-CH 2 NHCH 3 (IV) 6. Analysis of in pharmaceutical preparations The proposed was applied satisfactorily to the indirect determination of paracetamol in the following pharmaceutical preparations: with paracetamol 500mg; from Meheco (China). Paracetol with paracetamol 500mg; from S.D.I. (Iraq). Algesic with paracetamol 350mg, Codeine phosphate 10mg ; from S.D.I. (Iraq). Myogesic with paracetamol 450mg, orphenadrinecitrate 35mg; from Dar-Al-Dawa (Jordan). The concentrations of the PCT (as PAP) were calculated by direct measurements on the appropriate calibration graph. The results obtained are summarized in (Table2), and compared favorably to those reported by Al- Esawati (22) and the official (BP) (23). CONCLUSIONS Spectrophotometric procedure is proposed for the indirect determination of paracetamol in pharmaceutical preparations. The is based on the oxidative coupling reaction of paracetamol ( after acidic hydrolysis to form p- aminophenol) with phenylephrine hydrochloride using atmospheric oxygen as an oxidant in alkaline medium to form a water soluble, stable indophenol dye. The proposed has been applied successfully for the determination of paracetamol in some pharmaceutical preparations. REFERENCES Goodman-Hillman, A. Rall, T., Nier, A., and Taylor, P. (1996). The Pharmacology Basis Of Therapeutics. New York: McGraw-Hill. Prasanna R. B. (2009). Simultaneous RP-HPLC Determination Of Nimesulide And In Tablets. Int.J. ChemTech Res. 1(3), Akay, C., Dečim, I. T., Sayal, A., Aydin, A., Özkan, Y., and GUL, H., (2008). Rapid And Simultaneous Determination Of Acetylsalicylic Acid,, And Their Degradation And Toxic Impurity Products By HPLC In Pharmaceutical Dosage Forms. Turk J Med Sci, 38 (2), Uttam, D. P., Abhijit, V. N., Aruna, V. S., Tirumal, A. D., and Kiran, V. M. (2009). Simultaneous Determination Of Aceclofenac, And Chlorzoxazone By Hplc In Tablet Dose Form. E-Journal of Chemistry, 6(1),

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