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ISSN: 2161-0444
Medicinal chemistry
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Potentiometric and pHmetric Studies of Paracetamol

Swaroopa Rani N Gupta*

Department of Chemistry, Brijlal Biyani Science College, Amravati, Maharashtra, India

*Corresponding Author:
Swaroopa Rani N. Gupta
Department of Chemistry
Brijlal Biyani Science College
Amravati, Maharashtra, India
Tel: +919665041291
E-mail: [email protected]

Received date: January 11, 2015; Accepted date: January 23, 2016; Published date: January 25, 2016

Citation: Gupta SRN (2016) Potentiometric and pHmetric Studies of Paracetamol. Med chem 6:047-052. doi:10.4172/2161-0444.1000323

Copyright: © 2016 Gupta SRN. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Abstract

Acid-base titration of paracetamol in nonaqueous solvents was done. Procedure was followed for titration of paracetamol in different media like acetic acid, pyridine, dimethlformamide and ethyl alcohol with standard perchloric acid in glacial acetic acid, sodium ethoxide in ethyl alcohol using plantinum-calomel as well as glass-calomel electrode system. The equivalence point was located as accurately as possible by a differential graph of ΔE/ΔV or ΔpH/ΔV against V and concentration of test solution was computed. The acid-base titration of paracetamol is rapid and reproducible, and permits its determination in medicinal sample. The electrode systems vary with the solvent employed. The platinum-calomel electrode system is suitable where the solvent is glacial acetic acid in this case perchloric acid in glacial acetic acid is the titrant while the glass-calomel electrode system is suitable where the solvent is either pyridine, an alcohol or dimethyiformamide, the titrant consists of sodium ethoxide in ethyl alcohol.

Keywords

Acetic acid; Dimethlformamide; Ethyl alcohol; Paracetamol; Pyridine

Introduction

Paracetamol (acetaminophen) is one of the most popular analgesic and antipyretic drugs. Paracetamol is available in different dosage forms: tablet, capsules, drops, elixirs, suspensions and suppositories. Dosage forms of paracetamol and its combinations with other drugs have been listed in various pharmacopoeias [1,2]. The combination of paracetamol with dipyrone is used as an antipyretic, analgesic and anti-inflammatory drug. Numerous methods have been reported for the analysis of paracetamol and its combinations in pharmaceuticals or in biological fluids. Paracetamol has been determined in combination with other drugs using titrimetry [3,4], voltammetry [5], fluorimetry [6], colorimetry [6], UV-spectrophotometry [7-9], quantitative thin-layer chromatography (TLC) [10], high-performance liquid chromatography (HPLC) [11-16] and gas chromatography (GC) [17] in pharmaceutical preparations. Effect of electrophilic and electrodotic groups on the potentiometric titration of amides and other weak bases was studied [18]. Electrodotic groups enhance the potentiometric end point and electrophilic groups depress it, sometimes to the extent that the compound is not titratable. A combination of chloroform and acetic anhydride is a useful alternative medium for the titration of weak bases. A potentiometric method for determination of p-acetamidophenol was reported [19].

Analytical data are given for a representative number of amides, acetylated amines, and formylated amines [20]. In acetic acid, amides show little tendency toward salt formation with CH3COOH2+; however, upon addition of acetic anhydride, additional acidic species become evident and measurable end points are observed [21].

CH3COOH2 ++(CH3CO)2O ↔ (CH3CO)2–OH++CH3COOH ↔ CH3CO++(CH3COOH)2

Considerable evidence for this equilibrium has been presented by a number of investigators [21-25].

An accurate, simple, reproducible and sensitive method for the determination of paracetamol, caffeine and dipyrone was developed and validated [26].

In present study acid-base titration of paracetamol in nonaqueous solvents was done. Procedure was followed for titration of paracetamol in different media like acetic acid, pyridine, dimethlformamide and ethyl alcohol with standard perchloric acid in glacial acetic acid, sodium ethoxide in ethyl alcohol using plantinum-calomel as well as glass-calomel electrode system. The equivalence point was located as accurately as possible by a differential graph of ΔE/ΔV or ΔH/ΔV against V and concentration of test solution was computed.

Methodology

All chemicals were of A.R. grade. Solvents were purified before use. Medicinal samples of paracetamol were collected from local market of different make. OSAW direct reading potentiometer was used to carry out redox titrations using bright platinum wire and saturated calomel electrodes. The pH-titrations were made with an ELICO LI- 10 pH-meter in conjuction with Glass (EM-42) and calomel (ER-70) electrodes.

Acid-base titration of paracetamol in nonaqueous solvents was done by taking 0.2 g of Crocin paracetamol (Duphar) tablet in a 250 ml beaker and was dissolved in 25 ml of glacial acetic acid. A bright platinum wire electrode was dipped; the solution was connected to a calomel electrode via salt bridge and titrated with 0.1 N perchloric acid in acetic acid. Similar procedure was followed for titration of paracetamol in other media like pyridine, dimethlformamide and ethyl alcohol with standard sodium ethoxide in ethyl alcohol using plantinum-calomel as well as glass-calomel electrode system. The equivalence point was located as accurately as possible by a differential graph of ΔE/ΔV or ΔH/ΔV against V and concentration of test solution was computed.

Observation

Potentiometric methods embrace two major types of analyses: the direct measurement of an electrode potential from which the concentration of an active ion may be derived, and the changes in the electromotive force of an electrolytic cell brought about through the addition of a titrant. Two types of potentiometric titrations, Oxidation- Reduction and Acid-Base titrations in nonaqueous solvents, have been performed, and interest is focused upon changes in the e.m.f. of an electrolytic cell as a titrant of precisely known concentration is added to a solution of the analyte namely paracetamol.

Acid-base titration data for paracetamol against perchloric acid and C2H2ONa in different media - glacial acetic acid, pyridine, dimethyl formamide and ethyl alcohol are shown in Table 1.

Potentiometric Titration of Paracetamol in glacial acetic acid with 0.1 N HCIO4 in glacial acetic acid, using platinum - calomel electrodes
Volume of 0.1 N HCIO4, ml Potential,Volts Volume of 0.1 N HCIO4,  ml Potential,Volts
5 0.49 15 0.525
5.5 0.49 16 0.525
6 0.49 17 0.53
7 0.49 18 0.53
8 0.495 19 0.53
9 0.5 20 0.535
10 0.5 21 0.535
11 0.504 22 0.535
12 0.514 23 0.535
13 0.514 24 0.535
14 0.525 25 0.535
Potentiometric Titration of Paracetamol in pyridine with 0.075 N soldiumethoxide in ethyl alcohol, using platinum – calomel electrodes
Volume of 0.075 N C2H5ONa, ml Potential, Volts Volume of 0.075 N C2H5ONa,  ml Potential, Volts
4 0.22 15 0.279
5 0.22 16 0.293
6 0.225 17 0.305
7 0.225 18 0.314
8 0.232 19 0.317
9 0.232 20 0.317
10 0.232 21 0.326
11 0.239 22 0.326
12 0.243 23 0.326
13 0.249 24 0.326
14 0.26 25 0.326
Potentiometric Titration of Paracetamol in dimethylformamide with 0.075 N sodium ethoxide in ethyl alcohol, using platinum-calomel electrodes.
Volume of 0.075 N C2H5ONa, ml Potential, Volts Volume of 0.075 N C2H5ONa,  ml Potential, Volts
2 0.22 17 0.262
3 0.224 18 0.273
4 0.227 19 0.28
5 0.227 20 0.282
6 0.227 21 0.285
7 0.227 22 0.288
8 0.227 23 0.291
9 0.227 24 0.291
10 0.223 25 0.291
11 0.223 26 0.291
12 0.223 27 0.291
13 0.226 28 0.291
14 0.231 29 0.291
15 0.235 30 0.291
16 0.247    
Potentiometric Titration of Paracetamol in Pyridine with 0.09 N sodium ethoxide in ethyl alcohol.
Volume of 0.09 N C2H5ONa, ml Potential, Volts Volume of 0.09 N C2H5ONa, ml Potential, Volts
3 0.385 15 0.415
4 0.385 16 0.415
5 0.385 17 0.42
6 0.385 18 0.42
7 0.385 19 0.42
8 0.395 20 0.42
9 0.395 21 0.42
10 0.395 22 0.42
11 0.4 23 0.42
12.1 0.405 24 0.42
13 0.415 25 0.42
14 0.415    
Potentiometric Titration of Paracetamol in dimethyl formamide with 0.09 N sodium ethoxide in ethylalcohol.
Volume of 0.09 N C2H5ONa, ml Potential, Volts Volume of 0.09 N C2H5ONa, ml Potential, Volts
0.5 0.395 13 0.415
1 0.395 14 0.42
2 0.395 15 0.42
3 0.395 16 0.42
4 0.395 17 0.42
5 0.395 18 0.42
6 0.395 19 0.42
7 0.395 20 0.42
8 0.4 21 0.42
9 0.4 22 0.42
10 0.4 23 0.42
11 0.405 24 0.42
12 0.405 25 0.42
pH-metric Titration of Paracetamol in ethyl alcohol with 0.083 N sodium ethoxide in ethylalcohol.
Volume of 0.083 N C2H5ONa, ml pH Volume of 0.083 N C2H5ONa, ml Potential, Volts
4 12 14.5 13.3
5 12.1 15 13.4
6 12.15 16 13.5
7 12.25 17 13.6
7.5 12.3 18 13.65
8 12.4 19 13.7
9 12.5 20 13.75
10 12.6 21 13.75
11 12.7 22 13.8
12 12.8 23 13.8
13 12.9 24 13.8
14 13.2 25 13.85

Table 1: The acid-base titrations of paracetamol in nonaqueous solvents.

An end point is located more precisely by plotting successive values of the rate of change of cell e.m.f. vs each increment of titrant in the vicinity of the inflection point. The position of the maximum on the first derivative curve, Figures 1-6 corresponds to the inflection point on the normal titration curve.

medicinal-chemistry-Potentiometric-Titration-Paracetamol

Figure 1: Potentiometric Titration curves for Paracetamol in glacial acetic acid with 0.1 N HCIO4 in glacial acetic acid, using platinum - calomel electrodes.

medicinal-chemistry-Potentiometric-Paracetamol-pyridine

Figure 2: Potentiometric Titration curves for Paracetamol in pyridine with 0.075 N soldium ethoxide in ethyl alcohol, using platinum – calomel electrodes.

medicinal-chemistry-Potentiometric-dimethylformamide-sodium

Figure 3: Potentiometric Titration curves for Paracetamol in dimethylformamide with 0.075 N sodium ethoxide in ethyl alcohol, using platinum-calomel electrodes.

medicinal-chemistry-Titration-Paracetamol-pyridine

Figure 4: Potentiometric Titration curves for Paracetamol in Pyridine with 0.09 N sodium ethoxide in ethyl alcohol.

medicinal-chemistry-Paracetamol-dimethyl-formamide

Figure 5: Potentiometric Titration curves for Paracetamol in dimethyl formamide with 0.09 N sodium ethoxide in ethylalcohol.

medicinal-chemistry-Titration-Paracetamol-alcohol

Figure 6: pH-metric Titration curves for Paracetamol in ethyl alcohol with 0.083 N sodium ethoxide in ethyl alcohol.

Results and Discussion

The results of estimation of paracetamol by potentiometric method are represented in Table 2. It is found that paracetamol can be easily titrated by potentiometric method in nonaqueous media like glacial acetic acid with perchloric acid and in pyridine, dimethylformamide and ethyl alcohol with sodium ethoxide. Good inflection point is obtained, results are reproducible and recovery is nearly 100%.

S No Solvent Titrant Electrode system Inflection Point Weight of Tablet Amount of Paracetamol per Tablet, g
1 Glacial acetic acid 0.1 N HClO4 in acetic acid Platinum - Calomel 12.5 0.6 0.5 0.5669
2 Pyridine 0.075 N C2H5ONa in ethyl alcohol Platinum - Calomel 15 0.5915 0.5 0.5029
3 Dimethyl formamide 0.075 N C2H5ONa in ethyl alcohol Platinum - Calomel 16.5 0.5965 0.5 0.5579
4 Pyridine 0.09 N C2H5ONa in ethyl alcohol Glass - Calomel 12.5 0.6097 0.5 0.4997
5 Dimethyl formamide 0.09 N C2H5ONa in ethyl alcohol Glass - Calomel 12 0.6132 0.5 0.5
6 Ethyl alcohol 0.083 N C2H5ONa in ethyl alcohol Glass - Calomel 13.5 0.5875 0.5 0.4975

image

Table 2: Analysis of crocin (duphar) paracetamol tablet by potentiometric acid – base titration methods.

Acid-base reactions of paracetamol in nonaqueous solvents

Many acids or bases such as paracetamol that are too weak for determination in water become susceptible to titration in appropriate nonaqueous solvents. The major considerations in the choice of a solvent for acidimetric reactions are its acidity and basicity, its dielectric constant, and the physical solubility of a solute. Acidity is important because it determines to a large extent whether or not a weak acid can be titrated in the presence of a relatively high concentration of solvent molecules. Paracetamol, for example, cannot be titrated as an acid in aqueous solution because water is too acid and present in too high a concentration to permit the p-oxyacetanilide ion to be formed stoichiometrically by titration with a base. In other words the intrinsic basic strength of the p-oxyacetanilide ion and hydroxide ions are not sufficiently different for the reaction:

image

In less acid solvents, such as dimethylformamide or pyridine, this titration can be carried out readily with a stronger basic titrant, the alkoxide ion:

image

Acidic properties of solvent such as acetic acid produce a pronounced levelling effect on the weak base (p-hydroxyacetanilide) and thus it gets converted into strong base which then can be titrated with strong acid. The titrant is a solution of perchloric acid in glacial acetic acid which has been standardized with potassium hydrogen phthalate. In an analogous fashion, basic solvents enhance the properties of weak acid (p-oxyacetanilide). It produce distinctive end point in dimethylformamide. The titrant is sodium ethoxide. The electrode systems vary with the solvent employed. The platinumcalomel electrode system is suitable where the solvent is glacial acetic acid in this case perchloric acid in glacial acetic acid is the titrant while the glass-calomel electrode system is suitable where the solvent is either pyridine, and alcohol or dimethylformamide, the titrant consists of sodium ethoxide. Acid-Base reaction involved in case of paracetamol while titrating with perchloric acid/sodium ethoxide can be represented as follows.

image

Conclusion

Based on potentiometric studies of paracetamol it is concluded that the acid-base titration of paracetamol is rapid and reproducible, and permits its determination in medicinal sample. The electrode systems vary with the solvent employed. The platinum-calomel electrode system is suitable where the solvent is glacial acetic acid in this case perchloric acid in glacial acetic acid is the titrant while the glass-calomel electrode system is suitable where the solvent is either pyridine, an alcohol or dimethyiformamide, the titrant consists of sodium ethoxide in ethyl alcohol.

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Review summary

  1. Farida
    Posted on Sep 29 2016 at 7:09 pm
    This study was done in different solvents such as Glacial Acetic Acid, Pyrimidine, Ethanol and Dimethylformamide in which Paracetamol is highly soluble to calculate the Electromotive force.It would be better that author evaluate same study in water and isopropanol in which Paracetamol is less soluble to compare the inflection point. In general, this article is informative and provides useful and comprehensive information.
 

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