Research article · 2024 · Full text
International Journal of Advanced Chemistry ResearchSpectrophotometric method for determining Paracetamol in aqueous and pharmaceutical formulations using oxidation by potassium ferricyanide and coupling with sodium tungstate
Volume 6(2) · Pages 138–144 · DOI: 10.33545/26646781.2024.v6.i2b.238 ↗
Research areasAnalytical Methods in PharmaceuticalsChemical Thermodynamics and Molecular StructureThermal and Kinetic Analysis
Abstract
Author-writtenTo quantify paracetamol and its several medicinal formulations in an aqueous solution, a spectrophotometric approach was suggested. Paracetamol is oxidized by potassium ferricyanide and then coupled with sodium tungstate in a basic media as the basis for the procedure. The aqueous solution with a brown dye has the maximum absorption at 565 nm. It was discovered that the molar absorptivity was (2569.89 L/mol. cm) and that it complied with the law of beer between 1 - 65 µg/mL. The assay of pills, syrup, and ampules is accomplished with success using this technique.
Summary
Source-checkedPlain-language reading of the full paper, prepared with AI and checked against the text. Each point links to the authors' own words.
Why it matters
- Paracetamol is a widely used medication for treating pain and fever. View evidence ↗
- Improper storage of paracetamol formulations can lead to the formation of toxic substances such as p-aminophenol. View evidence ↗
- Spectrophotometric techniques are often used for drug analysis because they are easy to use and require readily available reagents and equipment. View evidence ↗
The question
- The study aimed to develop a spectrophotometric method to estimate paracetamol in aqueous pharmaceutical preparations using oxidation by potassium ferricyanide and coupling with sodium tungstate in an alkaline medium. View evidence ↗
What they did
- A paracetamol stock solution of 500 ppm was prepared and then diluted to create a concentration range of 1-70 µg/mL for analysis. View evidence ↗
- Sodium tungstate and potassium ferricyanide solutions were prepared at a concentration of 0.01M. View evidence ↗
- Alkaline solutions used in the process were prepared at a concentration of 1 M. View evidence ↗
- Interfering materials including starch, glucose, lactose, sucrose, and sodium benzoate were tested at concentrations of 40, 80, and 120 µg/mL. View evidence ↗
What they found
- The method demonstrated linearity between 1 and 65 µg/mL, with a molar absorptivity of 2569.89 L/mol.cm. View evidence ↗
- The method's accuracy was found to be between 96% and 102.6%, indicating high precision. View evidence ↗
- The presence of interfering substances did not affect the formation of the brown dye or the accuracy of the results. View evidence ↗
- The method achieved a detection limit of 0.229 µg/mL and a quantification limit of 0.764 µg/mL. View evidence ↗
What it means
- The authors conclude that the UV-Vis spectrophotometric method using oxidation and conjugation is a successful approach for paracetamol determination, offering good linearity and sensitivity. View evidence ↗
Visual summary
3 visualsIllustrations explain the paper; charts are replotted from the paper's own table values.
Chemical Process Flow
AI-generated conceptual illustration (Paracetamol molecules in a glass beaker). It explains the idea and does not show study data.
View source evidence ↗
Absorbance: 0.1 Ml vs 0.2 mL vs 0.3 mL vs 0.4 mL vs 0.5 mL
Replotted from Table 6 (page 3) of the original paper. Every bar is the paper's own table value.
View source evidence ↗
Absorbance: 5 vs 10 vs 15 vs 20 vs 25
Replotted from Table 8 (page 4) of the original paper. Every bar is the paper's own table value.
View source evidence ↗Figures & tables
From the original paper
Table 1
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Figure 1
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Table 15Introduction
One of the most well-known and often-used medications for fever and pain relief is paracetamol (Acetaminophen). Among analgesics, it holds a special place. Its IUPAC name is N-(4-hydroxyphenyl) acetamide, and its formula is C8H9NO2, with a molecular weight of 151.165 g.mol-1 (Scheme 1). Many kinds of paracetamol are available, and it is frequently taken with other drugs, such as cold medications. Typically, it is taken orally or intrarectally, but it can also be infused into a vein [1] .
Scheme 1:
The structure of paracetamol One essential component for the production of paracetamol is P-aminophenol. Additionally, it serves as an intermediate in the body's hydrolysis of paracetamol. One critical component for the production of paracetamol is P-aminophenol. Additionally, it serves as an intermediate in the body's hydrolysis of paracetamol [2,3] . paracetamol medicinal formulations may break down into toxic substances like p-aminophenol when stored improperly [4,5] . Numerous approaches were put proposed and documented in the literature to determine whether p-Amp was pure or the product of paracetamol's hydrolysis in an acidic or basic environment. Some of these techniques was HPLC [6,8] , electrochemical [9,10] , fluorescence [11] . Several spectrophotometric techniques have been employed because to their ease of use and the availability of several reagents and various devices that they require [12][13][14] . One of the most significant organic reactions with a variety of uses in analytical chemistry is oxidative coupling reactions.
The coupling of two organic molecules in the presence of an oxidizing agent under suitable conditions is necessary for oxidative coupling processes [2] . Diazotization of paminophenol resulted from hydrolysis of paracetamol then coupling with a various coupling agent such as 4 [(2-amino-1, 3thiazol-4-yl) amino] nitrobenzene [15] . A strong blue water-soluble dye is created when paracetamol and o-cresol undergo a direct reaction (oxidative-coupling reaction) in an alkaline media with sodium periodate present [16] , Oxidative coupling techniques have also been applied to N-(1-naphthyl) ethylenediamine dihydrochloride in the presence of potassium iodate [17] . Oxidation with N-Bromo succinimide and bleaching color of Eriochrome Black-T [18] , and the formation of Schiff bases also showed [19] . The present research included a spectrophotometric method for the estimation of Paracetamol in three pharmaceutical preparations in their aqueous solutions using the oxidation of Paracetamol by Potassium Ferricyanide (K.F) and coupling by the detector of Sodium Tungstate (STN) in an alkaline medium by Potassium hydroxide to produce brown dye.
Experimental Apparatus
PD-303 Spectrophotometer / Apel -Japan, Shimadzu UV Spectrophotometer (UV-1800) Japanese made with 1 cm quartz cells, Sartorius / M-Power sensitive balance Japan made.
Materials
The table below shows the chemicals used in this research, along with the manufacturer and their molecular weight.
Procedure
Procedure
Standard drug solution
The standard stock solution for Paracetamol (500 ppm) was prepared by dissolving (0.05 gm) of Paracetamol in 100 ml of distilled water, then the range of concentrations (1-70 µg/mL) were prepared by subsequent dilutions of the drug.
The reagent and oxidizer solutions
The reagent of Sodium tungstate (Na2WO4) (STN) and oxidizer of Potassium ferricyanide (K3Fe (CN)6) (K.F) solutions were prepared by dissolving (0.2938 gm, 0.3683 gm) respectively in 100 ml of distilled water each separately to obtain a concentration of 0.01M. The solutions were saved in a dark bottle.
The base solutions
The alkaline solutions used in this work were prepared by using a concentration of (1 M) per alkaline solution by dissolving the appropriate weights in (100 ml) of distilled water.
The solutions of interfering materials: Three increasing concentrations (40, 80, 120 µg/mL) of the interfering were prepared by dissolving the following weights respectively (0.001 0.002,0.003 gm) using glucose, Lactose, Sucrose, Starch, and Sodium benzoate each separately in a 25 mL bottle, fill to the mark by distilled water.
The pharmaceutical preparation solutions Tablets
Ten tablets of paracetamol were weighed and ground. Then precisely a weight of the mill was taken (0.0309 gm) dissolved in (100 mL) volumetric flask and fill the volume to the mark with distilled water to prepare (100 µg/mL) of paracetamol. This standard solution was used in the analytical applications of paracetamol.
Syrup and ampule
To prepare a concentration of 100 µg/mL of paracetamol pharmaceuticals (Syrup and ampule) a (1.0416, 0.208 mL) were taken and then moved to volumetric flasks of 50 mL separately.
The overlapping materials solutions
To prepare the standard solutions of (40, 80, 120 µg/mL) of each (Starch, glucose, lactose, sucrose, sodium benzoate) by using (0.001, 0.002, 0.003 gm) of each material separately to 25mL of volumetric flasks flask and fill the volume to the mark with distilled water.
Results and Discussion
For the subsequent experiments, 100 µg/mL of Paracetamol was taken using 25 mL volumetric flasks as a final volume and measured the absorbance and performed at 565 nm.
Principle of the method
This method includes the oxidation of Paracetamol by Potassium Ferricyanide (K.F) and coupling by the detector of Sodium Tungstate (STN) in an alkaline medium by Potassium hydroxide to produce brown dye.
Study of the optimum reaction condition:
Various variables were measured to find the best color intensity for the resulting color pigment according to the best-chosen conditions.
Study of select the best oxidizing agent
To find the best oxidizing had used for the oxidation process, (1 ml) of each of the different oxidizing agents was used separately to (1 ml) of the detector of sodium tungstate (STN) then adding (1 ml) of Paracetamol (500 µg/ml). Finally, add (1 ml) of potassium hydroxide in (25 ml) volumetric flasks complete the volume with distilled water to the mark and shake well. Potassium Ferricyanide gives the best color and best intensity, so it was chosen as the best oxidizing agent for this research.
Study of select the best volume of oxidizing agent
To find the best volume of oxidizing agent different sizes of Potassium ferricyanide were used ranging between (0.25 -4 ml) (0.01M), then add (1 ml) of the reagent of (0.01 M) Sodium tungstate. Finally, add (1 ml) of Paracetamol (500 ppm) and (1 ml) of (1M) Potassium hydroxide. Then we complete the volume of distilled water in 25 L volumetric flasks. The 1.7 ml of Potassium ferricyanide was chosen as the best volume because it gave the highest absorption.
Study of select the best volume of the reagent
Increasing volumes of the reagent of Sodium Tungstate (STN) were used at a concentration of (0.01 M), ranging between (0.1 -2 ml). (1.7 ml) (0.01M) of oxidizing agent Potassium Ferricyanide (K.F) was added, followed by the addition of (1 ml) of (500 ppm) of Paracetamol and (1ml) of (1M) Potassium hydroxide in (25 ml) volumetric flasks. The volume was completed to the mark with distilled water and well-shaken. It was found that the best volume of the detector (STN) is (0.4 ml).
Study of select the best volume of KOH
To measure the best volume of Potassium hydroxide, absorbents of several volumes ranged between (0.1 -1 ml). The (0.2 ml) was the best volume among the other because it gave the highest absorption and best color intensity.
Study of the effect of sequence of additions
To study the effect of the sequence of additions on the absorption and intensity of the resulting color, several sequences were taken. It was found that the best sequence is when the reagent is added first, followed by the oxidizing agent, then the drug, and finally, the base is added.
Study of effect of the time of oxidation
To study the effect of settling time on the absorption of the product from the oxidation process, appropriate sequences of additions were applied. The resulting dye of oxidation was stable for more than (50 minutes), while the best time for waiting for measure is (5 minutes).
°C 565nm
Final absorption spectra A brown dye was formed that gave the highest absorption at 565 nm. This dye is produced by the oxidation of Paracetamol by Potassium Ferricyanide (K.F) and coupling by the detector of Sodium Tungstate (STN) in an alkaline medium by Potassium hydroxide. Absorbance was measured using distilled water as a good solvent for this method.
Procedure and calibration graph
To find out the calibration graph for this research, (25 ml) volumetric flasks were used (0.4 ml) of (0.01 M) of the reagent Sodium tungstate (STN) was added to all volumetric flasks and then (1.7 ml) of (0.01M) the oxidant Potassium ferricyanide (K.F) was added. Later, increasing volumes of (500µg/ml) Paracetamol were added, ranging between (0.05 -3.75 ml). Finally, (0.2 ml) of 1 M) KOH was added to all volumetric flasks and made up to the mark with distilled water and shaken well. The resulting aqueous solutions of the dye were waited for (5 min) and then their absorbance was measured at (565 nm) against the blank. The resulting linearity limits ranged between (1 -65 µg/ml) and the molar absorptivity was (2569.89 L/mol. cm).
Accuracy and precision
To find the accuracy and precision found in this research, three different concentrations were proposed. The results for the accuracy values were very satisfactory and ranged between (96% -102.6%) and the precision was high. Nature of dye: To find out how the drug of Paracetamol is related to the reagent used, the Job method was applied. The resulting ratio for this work to the brown dye Paracetamol was (1:1).
Fig 3:
The application of Job`s method
The effect of interference: To study the effect of some interfering substances on the composition of the resulting brown dye, three different concentrations of them were used with a fixed concentration of Paracetamol. The solutions were used in final volumetric flasks of 25 ml and gave the same brown dye with high accuracy values.
Application of the method on the pharmaceutical dosage
The direct method was applied to three pharmaceutical preparations of Paracetamol in their aqueous solutions and all of them gave high accuracy values and satisfactory results. A concentration of 500 µg/ml of each pharmaceutical preparation was prepared and the method was applied in final (25 ml) volumetric flasks.
Conclusion:
The oxidation and conjugation were successfully applied to Paracetamol by spectrophotometric technique (Uv-vis). This procedure gave a good linearity which ranged between (1-65 µg/ml) and molar absorptivity equal to (2569.89 L/mol.cm) and Sandell`s index (0.05882 µg/ml). This method has been successfully applied to three types of pharmaceutical preparations. This proposed method gave high accuracy and high precision and gave a detection limit equal to (0.229 µg/ml) and a quantitative limit equal to (0.764 µg/ml).
Comparing the suggested approach to literature methods Other oxidative coupling reaction methods were compared with the suggested approach for estimating Paracetamol; the results are shown in the table.
Table 15:
The advantages and distinctions between the suggested approach and others in the literature are emphasized by this comparison.
Analytical parameter
Literature method (20) Literature method (2) Present
Figures and tables from the paper
| S. No. | Scientific name | Molar mass (gm/mol) | Chemical formula | Processing company |
|---|---|---|---|---|
| 1 | Paracetamol | 151.17 | C8H9NO2 | SDI |
| 2 | Sodium tungstate | 293.82 | Na2WO4 | SDI |
| 3 | Potassium ferricyanide | 329.24 | K3Fe(CN)6 | SDI |
| 4 | Sodium Iodate | 197.89 | NaIO3 | B.D.H |
| 5 | Potassium Permanganate | 158.04 | KMnO4 | B.D.H |
| 6 | Tris hydroxy methylamine | 121.136 | C4H11NO3 | Merck |
| 7 | Potassium dichromate | 294.185 | K2Cr2O7 | B.D.H |
| 8 | Potassium periodate | 230 | KIO4 | Merck |
| 9 | Potassium iodate | 214 | KIO3 | Aldrich |
| 10 | Potassium hydroxide | 56 | KOH | Merck |
| 11 | Sodium hydroxide | 40 | NaOH | Merck |
| 12 | Calcium hydroxide | 79.093 | Ca(OH)2 | Merck |
| 13 | Potassium carbonate | 138.205 | K2CO3 | B.D.H |
| 14 | Sodium carbonate | 106 | Na2CO3 | B.D.H |
| 15 | Potassium chromate | 194.18 | K2CrO4 | B.D.H |
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| Volumes of 0.1 M sodium tungstate | Absorbance |
|---|---|
| 0.1 mL | 0.201 |
| 0.2 mL | 0.181 |
| 0.3 mL | 0.168 |
| 0.4 mL | 0.230 |
| 0.5 mL | 0.197 |
| 0.6 mL | 0.192 |
| 0.7 mL | 0.183 |
| 0.8 mL | 0.192 |
| 0.9 mL | 0.186 |
| 1 mL | 0.188 |
| 1.2 mL | 0.182 |
| 1.4 mL | 0.192 |
| 1.6 mL | 0.187 |
| 1.8 mL | 0.172 |
| 2 mL | 0.174 |
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| No | Oxidizing agent 0.01 M | Color resulting |
|---|---|---|
| 1 | Sodium iodate | Colorless |
| 2 | Potassium Permanganate | Its color is light yellow and cloudy1 |
| 3 | Tris hydroxy methyl ammine | Colorless |
| 4 | Potassium dichromate | Its color is light yellow and cloudy |
| 5 | Potassium chromate | Its color is light yellow and cloudy |
| 6 | Potassium periodate | Colorless |
| 7 | Potassium iodate | Colorless |
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| The using base 1 M | Absorbance | Color |
|---|---|---|
| NaOH | 0.185 | Orange brown |
| Ca(OH)2 | 0.173 | Very light yellow color |
| KOH | 0.230 | Dark brown color |
| K2CO3 | 0.074 | Very light yellow color |
| Na2CO3 | 0.051 | Very light yellow color |
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| Volumes of 0.1 M Potassium Ferricyanide | Absorbance |
|---|---|
| 0.1 mL | 0.003 |
| 0.2 mL | 0.016 |
| 0.3 mL | 0.034 |
| 0.4 mL | 0.038 |
| 0.5 mL | 0.046 |
| 0.6 mL | 0.033 |
| 0.7 mL | 0.041 |
| 0.8 mL | 0.041 |
| 0.9 mL | 0.054 |
| 1 mL | 0.055 |
| 1.2 mL | 0.156 |
| 1.3 mL | 0.182 |
| 1.4 mL | 0.202 |
| 1.5 mL | 0.213 |
| 1.6 mL | 0.187 |
| 1.7 mL | 0.725 |
| 1.8 Ml | 0.560 |
| 1.9 mL | 0.521 |
| 2 mL | 0.346 |
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| Volumes of 0.1 M KOH | Absorbance |
|---|---|
| 0.1 Ml | 0.218 |
| 0.2 mL | 0.242 |
| 0.3 mL | 0.205 |
| 0.4 mL | 0.198 |
| 0.5 mL | 0.185 |
| 0.6 mL | 0.203 |
| 0.7 mL | 0.242 |
| 0.8 mL | 0.195 |
| 0.9 mL | 0.198 |
| 1 mL | 0.208 |
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| Order | Sequence | Absorbance |
|---|---|---|
| 1 | K.F + STN +D + B | 0.218 |
| 2 | STN + K.F + D + B | 0.242 |
| 3 | D + STN +K.F + B | 0.205 |
| 4 | D + K.F + STN + B | 0.198 |
| 5 | K.F + D + STN + B | 0.185 |
| 6 | STN + D + K.F + B | 0.203 |
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| Time | Absorbance |
|---|---|
| 5 | 0.310 |
| 10 | 0.308 |
| 15 | 0.302 |
| 20 | 0.286 |
| 25 | 0.270 |
| 30 | 0.258 |
| 35 | 0.240 |
| 40 | 0.235 |
| 45 | 0.220 |
| 50 | 0.201 |
| One hour | 0.188 |
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| Amount taken µg/mL | Abs | Amount found µg/Ml | Rec% | Avg of Rec% | RSD |
|---|---|---|---|---|---|
| 7 | 0.610 | 6.74 | 96% | 96% | 0.0007% |
| 7 | 0.610 | 6.74 | 96% | ||
| 7 | 0.611 | 6.8 | 97% | ||
| 25 | 0.934 | 25.8 | 103% | 102.6% | 0.0083% |
| 25 | 0.930 | 25.5 | 102% | ||
| 25 | 0.929 | 25.5 | 102% | ||
| 40 | 1.162 | 39 | 98% | 97% | 0.00094% |
| 40 | 1.157 | 38.97 | 97% | ||
| 40 | 1.157 | 38.97 | 97% |
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| Interferences | Conc. µg/mL | Conc. Taken of paracetamol µg/mL | Abs | Conc. Found of paracetamol µg/mL | Rec% |
|---|---|---|---|---|---|
| Glucose | 40 | 25 | 0.930 | 25.4 | 101% |
| 80 | 25 | 0.928 | 25.5 | 102% | |
| 120 | 25 | 0.928 | 25.5 | 101% | |
| Lactose | 40 | 25 | 0.931 | 25.6 | 102% |
| 80 | 25 | 0.929 | 25.5 | 102% | |
| 120 | 25 | 0.930 | 25.4 | 101% | |
| Sucrose | 40 | 25 | 0.925 | 25.2 | 101% |
| 80 | 25 | 0.930 | 25.4 | 101% | |
| 120 | 25 | 0.927 | 25.3 | 101% | |
| Starch | 40 | 25 | 0.925 | 25.2 | 101% |
| 80 | 25 | 0.929 | 25.5 | 102% | |
| 120 | 25 | 0.928 | 25.4 | 101% | |
| Sodium benzoate | 40 | 25 | 0.920 | 24.9 | 99.9% |
| 80 | 25 | 0.920 | 24.9 | 99.9% | |
| 120 | 25 | 0.925 | 25.2 | 101% |
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| Drug | Pharmaceutical content | Concentration | Company |
|---|---|---|---|
| Paracetamol | Paracetamol tablets | 500 mg | Aswar AL-Khaleej Company |
| Paracetamol | Antipyrol syrup | 120 mg /5 ml | SDI -Iraq |
| Paracetamol | Paracetamol ampule | 600mg / 5 ml | SDI -Iraq |
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| Pharmaceutical Formula | Conc. Taken of paracetamol µg/mL | Conc. Found of paracetamol µg/mL | Rec% | Avg. Rec% |
|---|---|---|---|---|
| Tablets 500 mg | 10 | 9.68 | 96% | 96.6% |
| 30 | 29.38 | 97% | ||
| 50 | 48.5 | 97% | ||
| Ampule 500mg/ 5ml | 10 | 9.68 | 96% | 97% |
| 30 | 29.27 | 97% | ||
| 50 | 49.56 | 99% | ||
| Syrup 120 mg/ 5ml | 10 | 10.3 | 103% | 101% |
| 30 | 29.5 | 98% | ||
| 50 | 51.4 | 102% |
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| Analytical parameter | Literature method (20) | Literature method (2) | Present method |
|---|---|---|---|
| Reagent | Copper sulphate | Methyldopa | Sodium tungstate |
| Beers law | (2-100) µg/ml | (10-100) µg/ml | (1-65) µg/ml |
| λ max | 520 nm | 580 nm | 565 nm |
| Molar absorption coefficient | 8.61 * 10 2 L/mol.cm | 7.75 * 10 3 L/mol.cm | 2569.89 L/mol.cm |
| Solvent | Distilled water | Distilled water | Distilled water |
| Recovery | 99.2% | 98.9% | 98.5% |
| RSD | 0.484 | 0.9961 | 0.0033 |
| Sandell index | 6.62 * 10 -6 µg/ml | ---------- | 0.05882 µg/ml |
| pharmaceutical preparation | Tablets | Tablets, Syrup, Ampule | Tablets, Syrup, Ampule |
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