Effect of Supporting Electrolytes on Polarographic Anodic Waves of

Paracetamol

Swaroopa Rani N. Gupta 1

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

Abstract. Paracetamol an analgesic and antipyretic drug determination in pharmaceuticals is important,

since an overdose of paracetamol can cause toxic effects. The aim of present study is to study effect of

supporting electrolytes on polarographic anodic waves of paracetamol so that these data can be utilized for

development of procedures for their quantitative estimations and applications to various pharmaceutical

preparations. Effect of suppporting electrolyte HCIO4, CH3COOH, HCI, Borate buffer, H2SO4 and NNO3 on

polarographic wave of paracetamol in presence of different maxima suppresors gelatin, fuchsin, methyl red,

bromocresol green, cellosolve, salicylic acid, thymol blue, methyl thymol blue, bromophenol red were

studied.

Keywords: paracetamol, HCIO4 , CH3COOH, HCI, borate buffer, H2SO4, HNO3.

1. Introduction

Bosch et al (2006) evaluated the utility of different techniques for quantification of paracetamol content

in pharmaceutical formulations and biological samples [1]. Many methods for determination of paracetamol

had been described in literature, including chromatography (RP - HPLC) [2], chemometric-assisted

spectrophotometric [3], spectroscopy [4]-[6]. The review was described about some qantitative estimation of

Paracetamol and Lornoxicam in bulk and tablet formulation. The quantitation was carried out by

simultaneous equation method, absorption ratio method, stability indicating reversed phase high performance

liquid chromatographic method, Reverse Phase High Performance Liquid Chromatographic method, and

High Performance Thin Layer Chromatography method. All the methods were validated [7]. A simple,

selective, accurate RP-HPLC method was developed and validated for the analysis of paracetamol,

phenylephrine hydrochloride and loratadine in commercially available tablet formulations [8]. A simple,

precise, and accurate reversed-phase liquid chromatographic method has been developed for the

simultaneous determination of paracetamol (PCM), chlorzoxazone (CHZ), and nimesulide (NIM) in

pharmaceutical dosage form [9]. Two simple, accurate and reproducible methods were developed and

validated for the simultaneous determination of paracetamol (PARA) and pamabrom (PAMB) in pure form

and in tablets. The first method was based on reserved-phase high-performance liquid chromatography, and

the second method was based on thin-layer chromatography [10]. UV-Spectrophotometry and RP-HPLC

methods were validated for the simultaneous analysis of acetaminophen in marketed tablets (Olufemi et al.,

2013).

Paracetamol is a common analgesic and antipyretic drug that is used for the relief of fever, headaches

and other minor aches and pains. Their determination in pharmaceuticals is of paramount importance, since

an overdose of paracetamol can cause toxic effects. The aim of the present study is to study effect of

supporting electrolytes on polarographic anodic waves of paracetamol so that these data can be utilized for

development of procedures for their quantitative estimations and applications to various pharmaceutical

preparations.

Corresponding author. Tel.: + 919665041291.

E-mail address: swargupta@yahoo.com.

2014 3rd International Conference on Environment, Chemistry and Biology

IPCBEE vol.78 (2014) © (2014) IACSIT Press, Singapore

DOI: 10.7763/IPCBEE. 2014. V78. 12

61

Fig. 1: Effect of HClO4 concentration on the anodic wave of 2.0 x 10

-5 M Paracetamol in presence of 0.008 % Gelatin

Fig. 2: Effect of HClO4 concentration on the anodic wave of 1.0 x 10

-4 M Paracetamol in presence of 3.75 x 10

-4 %

Fuchsin

2. Methodology

The effect of suppporting electrolyte HCIO4, CH3COOH, HCI, Borate buffer, H2SO4 and HNO3 on

polarographic wave of paracetamol in presence of different maxima suppresors gelatin, fuchsin, methyl red,

romocresol green, cellosolve, salicylic acid, thymol blue, methyl thymol blue, bromophenol red were studied.

Systems were prepared containing an aliquot of paracetamol solution, different amount of maxima

62

suppressors and supporting electrolyte. 50 ml total volume was maintained for each measurement.

Polarogram of each system were recorded on D.C. Recording polarograph with OmniScribe recorder

between 400 to 1400 mV using Rotating Platinum micro Electrode (RPE) as anode and Saturated Calomel

Electrode (S.C.E.) as cathode.

3. Results and Discussion

Effect of different supporting electrolyte i.e. HCIO4 , CH3COOH, HCI, Borate buffer, H2SO4, and HNO3

concentration on current – voltage curve of paracetamol are shown in Fig. 1 to 14. Increasing concentrations

of different supporting electrolytes are found to increase paracetamol wave height.

Fig. 3: Effect of CH3COOH concentration on the anodic wave of 2.0 x 10

-5 M Paracetamol in presence of 0.008 %

Gelatin

Fig. 4: Effect of CH3COOH concentration on the anodic wave of 8.0 x 10

-5 M Paracetamol in presence of 5 x 10

-5 %

63

Fuchsin

Fig. 5: Effect of CH3COOH concentration on the anodic wave of 1.0 x 10

-3 M Paracetamol in presence of 1 x 10

-3 %

Methyl red

Fig. 6: Effect of CH3COOH concentration on the anodic wave of 7.5 x 10

-4 M Paracetamol in presence of 1.5 x 10

-3 %

Thymol blue

64

Fig. 7: Effect of CH3COOH concentration on the anodic wave of 6.0 x 10

-4 M Paracetamol in presence of 2.5 x 10

-2 %

Bromocresol green

Fig. 8: Effect of HCl concentration on the anodic wave of 1.5 x 10

-4 M Paracetamol in presence of 1.5 x 10

-3 % Fuchsin

65

Fig. 9: Effect of HCl concentration on the anodic wave of 1.0 x 10

-4 M Paracetamol in presence of 2.5 x 10

-4 % Methyl

red

Fig. 10: Effect of HCl concentration on the anodic wave of 1.0 x 10

-4 M Paracetamol in presence of 1.25 x 10

-3 %

Thymol blue

66

Fig. 11: Effect of HCl concentration on the anodic wave of 1.0 x 10

-4 M Paracetamol in presence of 3.78 x 10

-3 %

Bromocresol green

Fig. 12: Effect of Borate buffer of different pH on the anodic wave of 3.0 x 10

-4 M Paracetamol in presence of 2.5 x 10

-

5 % Fuchsin

67

Fig. 13: Effect of H2SO4 concentration on the anodic wave of 3.0 x 10

-5 M Paracetamol in presence of 1.25 x 10

-2 %

Fuchsin

Fig. 14: Effect of HNO3 concentration on the anodic wave of 6.0 x 10

-5 M Paracetamol in presence of 1 x 10

-3 %

Fuchsin

3.1. Effect of perchloric acid on the anodic waves of paracetamol

Effect of various concentrations of perchloric acid on the anodic waves of paracetamol in presence of

0.008 % gelatin/3.75 x 10-4

% fuchsin as maxima suppressors is evident from Fig. 1 and 2. Good sigmoid

C-V curves all starting at about 650-700 mv are obtained. The apparent diffusion currents of very small

concentration of oxidizable substance i.e. paracetamol increase markedly with increasing applied e.m.f., and

when the proper correction is applied for the residual current the corrected diffusion current is found to be

practically constant in case of gelatin as maxima suppressor. However in case of fuchsin this correction does

not produce a constant limiting current, indicating that the limiting current is not entirely diffusion controlled.

It is seen that the residual current increases markedly with increasing concentration of perchloric acid from

68

0.1 M to 3 M. The increase in residual current is attributed to the increase in the condenser current resulting

from the charging of the double layer at the surface of R.P.E. With further increase in its concentration upto

7 M decrease in residual currents are observed where the capacity of the double layer changes markedly. In

case of gelatin, at the former concentrations of perchloric acid, the waves has a flat slope and the diffusion

current corrected for the residual current of the blank solution found to decrease slightly due to decrease in

the apparent diffusion coefficient as perchloric acid concentration changes from 0.1 to 3 M. At higher

concentration (> 3 M) of HCIO4, the slope of waves becomes much flat which is indicative of irreversible

reaction and wave height decreases considerably may be due to pronounced increasing character of viscosity.

In case of fuchsin, in addition to increase in residual current due to rise in charging current with variation of

HCIO4 concentration from 0.001 to 3 M they also increases wave height considerably. Increase of limiting

current is caused by streaming of the solution which occurs over a wide potential range of the limiting

current. Therefore the current rises above the diffusion controlled value over a wide range. Vigorous motion

(streaming) of the solution is suppressed by gelatin and not by fuchsin hence in previous case an increase in

wave height (due to streaming motion) with changing HCIO4 concentration from 0.14 to 2.76 M is not

observed.

3.2. Effect of acetic acid on the anodic waves of paracetamol Effect of various concentrations of acetic acid on the anodic wave of paracetamol in presence of 0.008 %

gelatin, 5 x 10-5

% fuchsin, 1 x 10-3

% methyl red, 1.5 x 10-3

% thymol blue and 2.5 x 10-2

% bromocresol

green as maxima suppressors, shown in Fig. 3 to 7, are found to show no markable change in residual current.

Decomposition oxidation potential is found to remain constant ( 600 – 700 mv). In the dilute acetic acid

medium the diffusion current appeared to be smaller than in concentrated acetic acid. This difference is due

to the fact that the diffusion coefficient of paracetamol in dilute acetic acid is smaller than in concentrated

acetic acid. In case of gelatin diffusion current as well as nature of C-V curve remains constant as acetic acid

concentration changes from 0.0012 to 2.93 M. Current increases at fairly positive potentials, but no limiting

current plateau is observed and the wave coincides with the curve of blank; indicating no restriction in the

rate at which the participant (depolarizer) in the electrode process can be brought to the surface of the R.P.E.

This is because supporting electrolyte i.e. acetic acid causes depolarization of the R.P.E. before the widest

possible potential range of paracetamol reaches. In case of fuchsin, methyl red, thymol blue and

bromocresol green as maxima suppressors markable rise in diffusion current values are noticed with

increasing concentrations of acetic acid. Good sigmoid curves are obtained over a 4000 fold range acetic

acid. For lower concentrations of acetic acid the waves have a flat slope and the diffusion current remained

constant until the wave of supporting electrolyte appeared. But for higher concentrations of it waves became

fairly steep making limiting current region indistinguishable.

3.3. Effect of hydrochloric acid on the anodic waves of paracetamol In hydrochloric acid solutions of paracetamol, catalytic waves are observed as may be seen in presence

of 1.5 x 10-3

% fuchsin, 2.5 x 10-4

% methyl red and 1.25 x 10-3

% thymol blue (Fig. 8 to 10). Catalytic

processes are manifested by a separate wave at potentials more positive than the wave for the oxidation of

paracetamol as in case of 0.5 to 1.5 M HCI in presence of 1.5 x 10-3

% fuchsin. Only one wave appears at <

0.5 M HCI. At 0.5 M HCI a coalescence of two waves occurs, these waves separate at higher concentration

values of HCI. Catalytic waves are characterized by a non-linear dependence on the paracetamol

concentration and function of pH and increase with increasing HCI concentration. Thus in addition to

oxidation processes polarographic curves also indicates catalytic processes. The apparent diffusion currents

often increase markedly with increasing applied e.m.f. This is due to the increase of the residual current with

increasing applied e.m.f. Further it is seen that the residual current increases with increasing HCI

concentration from 0.001 to 0.05 M HCI. The effect of HCI in presence of 3.78 x 10-3

% bromocresol green

is particularly different. The height and shape of the wave depends on the concentration of the hydrochloric

acid. The slope of the rising portion of the wave depends on the resistance of the solution. In very dilute

solutions ( 0.01 M), which have a high resistance, the wave is flat and the current increases less steeply

with increasing applied voltage. In more concentrated solutions the height of the wave decreases due to the

reason that the diffusion coefficient of the paracetamol in concentrated HCI solution was smaller than that in

69

dilute hydrochloric acid medium. The shift of the waves to more positive potentials with increasing

concentration of hydrochloric acid is also noticed in Fig. 11 (Edecom. = 600 mV at 0.001 M HCI; Edecom. = 725

mV at 3 M HCI). 1 M HCI containing 3.78 x 10-3% bromocresol green is found to be an optimum

supporting electrolyte in which case the diffusion current as well as limiting current plateau is well

developed before the wave of supporting electrolyte appeared.

3.4. Effect of borate buffer on the anodic waves of paracetamol Effect of borate buffer of different pH is shown in Fig. 12. At the former pH values two-step waves are

found. The “depolarization potential” at the beginning of the first wave is found to shift 50 mv to more

negative potentials with a unit increase in pH. Edecom at pH 8, 9, 10 and 11 is found to be 300, 250, 200 and

200 mv respectively. At pH value of 11 only one wave is found. At a pH of 9 the first diffusion current is

about equal to the total diffusion current found at lower pH values, the second wave comprising only a few

percent of the total current. In a more alkaline medium the second wave increases. At a pH of 10 two waves

of nearly equal height are found.

In solutions containing free sodium hydroxide the diffusion current decreases with time since the red

form of fuchsin is changed into the colourless carbional which probably has stronger adsorbability hence

more it suppresses the wave. The polarographic method is found quite suitable for following the rate of

colour fading of fuchsin in an alkaline medium. When the concentration of red form becomes so small that

only one wave is obtained, all the colourless form now remains adsorbed.

Basic Fuchsin Colourless Carbinol

In buffered solutions of paracetamol, catalytic waves are observed. Catalytic processes are manifested

by a separate wave at potentials more positive than the wave for the oxidation of paracetamol. Catalytic

waves are characterized by a non-linear dependence on the paracetamol concentration. In buffered solutions,

catalytic waves are found to increase with increasing buffer concentration.

3.5. Effect of Sulphuric acid on the Anodic Waves of Paracetamol

In addition to increase in residual current, an increase in limiting current above the diffusion controlled

value due to increase in the apparent diffusion coefficient is observed with increasing concentrations of

sulphuric acid. The diffusion current remained constant until the wave of the supporting electrolyte appeared

(Fig. 13).

3.6. Effect of Nitric acid on the Anodic Waves of Paracetamol Similar results as described above are obtained with varying concentrations of HNO3 in presence of 1 x

10-3

% fuchsin. The residual as well as diffusion current increases markedly as nitric acid concentration

changes from 0.01 to 2 M (Fig. 14). At higher concentrations of it residual current of the supporting

electrolyte alone predominates than that of diffusion current.

4. Conclusion

The residual current increases markedly with increasing concentrations of perchloric aicd from 0.1 to 3

M (in presence of optimum concentration of gelatin / fuchsin). With further increase in its concentration

upto 7 M decreases in residual currents are observed where the capacity of the double layer changes

markedly. In case of gelatin at the former concentrations of perchloric acid the diffusion current decreases

slightly due to decrease in the apparent diffusion coefficient. At higher concentration (> 3M) of HCIO4,

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wave height decreases considerably may be due to pronounced increasing character of viscosity. While in

case of fuchsin, variation of perchloric acid concentration from 0.001 to 3 M increases wave height

considerably.

Effect of various concentrations of acetic acid on the anodic wave of paracetamol in presence of

optimum concentration of gelatin, fuchsin, methyl red, thymol blue and bromocresol green as maxima

suppressors is found to show no markable change is residual current. Decomposition oxidation potential is

found to remain constant. ( 600-700 mV). In the dilute acetic acid medium the diffusion current appeared to

be smaller than in concentrated acetic acid. This difference is due to the fact that the diffusion coefficient of

paracetamol in dilute acetic acid is smaller than in concentrated acetic acid.

In hydrochloric acid solutions of paracetamol in addition to oxidation processes polarographic curves

also indicate catalytic processes. The shift of the waves to more positive potentials with increasing

concentration of hydrochloric acid is also noticed.

The depolarization potential is found to shift, 50 mV to more negative potentials with a unit increase in

pH. In solutions containing free sodium hydroxide the diffusion current decreases with time since the red

form of fuchsin is changed into the colourless carbinol form which probably has stronger adsorbability hence

more it suppresses the wave.

In addition to increase in residual current, an increase in limiting current above the diffusion controlled

value due to increase in the apparent diffusion coefficient is observed with increasing concentrations of

sulphuric acid. Similar results are obtained with varying concentrations of nitric acid.

Maxima suppressor-Supporting electrolyte combinations as shown in Table 1 were found to give good

results and were used for further determination of paracetamol.

Table 1: Optimum concentration of Maxima Suppressor-Supporting Electrolyte for Paracetamol determination.

Maxima Suppressor Supporting

electrolyte Maxima Suppressor

Supporting

electrolyte

8 x 10-3

% Gelatin 0.14 M HCIO4 1.5 x 10-3

% Fuchsin 0.1 M HCI

3.75 x 10-4

% Fuchsin 0.1 M HCIO4 2.5 x 10-4

% Methyl red 0.01 M HCI

1 x 10-6

% Gelatin 0.1 M CH3COOH 1.25 x 10

-3 % Thymol

blue 1.0 M HCl

5 x 10-5

% Fuchsin 0.1 M CH3COOH 3.78 x 10

-3 %

Bromocresol green 1.0 M HCl

1 x 10-3

% Methyl red 0.1 M CH3COOH 2.5 x 10-5

% Fuchsin Borate Buffer of

pH 10

1.5 x 10-2

% Thymol

blue 2.0 M CH3COOH 1.25 x 10

-2 % Fuchsin 0.99 M H2SO4

2.5 x 10-2

%

Bromocresol green 1.0 M CH3COOH 1 x 10

-3 % Fuchsin 0.1 M HNO3

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