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SPECTROPHOTOMETRIC DETERMINATION OF PARACETAMOL USING ZIRCONIUM (IV) OXIDE AND AMMONIUM TRIOXOVANADATE (V)

TABLE OF CONTENTS

Title page ————————————————————————– i

Certification———————————————————————– ii

Dedication ———————————————————————— iii

Acknowledgment—————————————————————– iv

Table of Contents —————————————————————- v

List of Tables———————————————————————- vi

List of Figures——————————————————————— vii

Abstract —————————————————————————- viii

 

CHAPTER ONE

1.0 Introduction —————————————————————– 1

1.1 Ultraviolet – visible spectrophotometry (UV – visible

spectrophotometry).——————————————————– 1

1.2 Paracetamol —————————————————————— 4

1.3 The structure of paracetamol——————————————— 5

1.4 Mechanism of action of paracetamol———————————– 6

1.5 Metabolism —————————————————————— 10

1.6 Medical uses of paracetamol ——————————————— 10

1.7 Adverse effects/toxicity ————————————————— 11

1.8 Statement of the problem ———————————————— 12

1.9 Objectives of the study—————————————————– 13

CHAPTER TWO:

2.0 Literature review———————————————————— 14

2.1 A brief historical background of paracetamol———————— 14

2.2 Methods of determining paracetamol.———————————- 17

2.2.1   Chromatographic methods of determination——————— 17

2.2.2   UV-Visible spectrophotometric methods————————— 21

2.2.3   Fluorescence spectrometric methods——————————- 27

2.3   Spectrophotometric determination of the stoichiometry of

metal to ligand in a complex——————————————— 30

CHAPTER THREE

3.0 Materials and methods —————————————————- 33

3.1 Materials ——————————————————————— 33

3.1.1   Aparatus/Equipment————————————————– 33

3.2.0   Preparation of Reagents ———————————————- 33

3.2.1   Preparation of 0.1 M paracetamol———————————– 33

3.2.2   Preparation of 0.1 M Zirconium(IV) oxide, (Zirconia)———– 33

3.2.3   Preparation of 0.1 M ammonium trioxovanadate(V)———— 34

3.3.0   Absorption spectra—————————————————— 35

3.3.1   Absorption spectrum of paracetamol——————————- 35

3.3.2 Absorption spectrum of zirconium(IV) in sodium hydroxide

Medium———————————————————————- 35

3.3.3.   Absorption spectrum of mixture of paracetamol and Zr(IV)

in sodium hydroxide medium—————————————- 36

3.3.4   Absorption spectrum of vanadium(V) in

tetraoxosulphate(VI) acid medium———————————— 36

3.3.5   Absorption spectrum of mixture of paracetamol and

vanadium(V) in tetraoxosulphate(VI) acid medium————– 36

3.4.0   Determination of the stoichimetry of the reactions

between paracetamol and the oxidants—————————– 37

3.4.1 Stoichiometry of reaction between paracetamol and

zirconium(IV)————————————————————- 37

3.4.2   Stoichiometry of reaction between paracetamol and

vanadium(V)————————————————————– 37

3.5.0   Determination of optimal conditions——————————- 38

3.5.1 Effect of pH on Zr(IV)-paracetamol reaction———————— 38

3.5.2   Effect of pH on V(V)-paracetamol reaction————————- 38

3.5.3   Effect of time on the reaction of paracetamol with

zirconium(IV)————————————————————- 38

3.5.4   Effect of time on the reaction of paracetamol with V(V)——– 39

3.5.4   Effect of temperature on the reaction paracetamol with

Zirconium(IV)————————————————————- 39

3.5.6   Effect of temperature on the reaction of paracetamol

with vanadium(V) ——————————————————– 39

3.6.0    Beer’s calibration plots———————————————– 39

3.6.1   Calibration curve for paracetamol-Zr(IV) reaction————— 39

3.6.2   Calibration curve for paracetamol-V(V) reaction—————– 40

3.7.0   Quantitative assay of the drugs————————————- 40

3.7.1   Assay of paracetamol with Zirconium(IV)————————- 40

3.7.2   Assay of paracetamol with vanadium(V)————————— 41

CHAPTER FOUR

4.0   Results and discussion————————————————– 42

4.1   Absorption spectrum of paracetamol.——————————— 42

4.2   Absorption spectrum of zirconium(IV) in NaOH medium.——- 42

4.3   Absorption spectrum of a mixture of paracetamol and

zirconium(IV) in NaOH medium ————————————— 42

4.4   Absorption spectrum of vanadium(V)

in tetraoxosulphate(VI) acid medium ——————————— 47

4.5   Absorption spectrum of the product of paracetamol-V(V)

reaction in H2SO4 medium ———————————————- 47

4.6.1   Stoichiometry of reaction between paracetamol and Zr(IV)— 49

4.6.2   Stoichiometry of reaction between paracetamol and

vanadium(V)————————————————————– 50

4.7.0   Effect of pH on the reaction of paracetamol and Zr(IV)——— 51

4.7.1   Effect of pH on paracetamol-V(V) reaction————————- 52

4.7.2   Effect of time on the reaction of paracetamol with Zr(IV)—— 53

4.7.3   Effect of time in the reaction of paracetamol with

vanadium(V)————————————————————– 54

4.7.4   Effect of temperature on paracetamol-Zr(IV) reaction———– 55

4.7.5   Effect of temperature on paracetamol-vanadium(V) reaction- 56

4.8   Beer’s calibration plot for the reaction of paracetamol

with zirconium(IV)——————————————————— 57

4.8.2   Beer’s calibration plot for the reaction of paracetamol

with vanadium(V)——————————————————— 58

4.9.0   Validation of paracetamol in dosage form with zirconium(IV)-59

4.9.1   Validation of paracetamol in dosage with vanadium(V)——– 60

CHAPTER FIVE

Conclusion———————————————————————— 61

References————————————————————————- 62

 

 

LIST OF TABLES

4.6   The mole ratio of [paracetamol]/ [Zr(IV)] and absorbance. —— 49

4.7:  The mole ratio of [paracetamol]/ [V(V)] and absorbance——— 50

4.8: Effect of pH on Zr(IV)- paracetamol reaction.———————— 51

4.9: Effect of pH on V(V)-paracetamol reaction.—————————   52

4.9: Effect of pH on V(V)-paracetamol reaction.—————————   52

4.10: Effect of Time on Paracetamol-Zr(IV) reaction———————-   53

4.11: Effect of time on paracetamol – V(V) reaction———————-   54

4.12:  Effect of temperature on paracetamol-Zr(IV) reaction————   55

4.13:  Effect of temperature on paracetamol-V(V) reaction————-   56

4.14 – Beer’s calibration plot for paracetamol-Zr(IV) reaction———   57

4.15: Beer’s calibration plot for paracetamol-V(V) reaction————-   58

4.16: Analysis of paracetamol (commercial brand) ———————-   59

4.17:  Analysis of paracetamol (commercial brand)———————-   60

4.18:  Spectral characteristics and analytical data of

paracetamol with Zr(IV) and V(V)————————————- 60

FIGURES/SCHEMES

4.1   UV spectrum of paracetamol ——————————————- 44

4.2   UV spectrum of zirconium(IV) in NaOH medium —————— 45

4.3   UV spectrum of mixture of paracetamol and

zirconium(IV) NaOH medium——————————————- 46

4.4 UV spectrum of V(V) in H2SO4 medium ——————————- 47

4.5   UV spectrum of mixture of paracetamol and V(V) in

H2SOmedium ————————————————————-  48

4.6 Absorbance Vs mole ratio for paracetamol-Zr(IV) reaction——— 49

4.7   Absorbance Vs mole ratio for paracetamol and V(V)————— 50

4.8   Abs-pH relationship for paracetamol-Zr(IV) reaction————– 51

4.9   Abs-pH relationship for paracetamol-V(V) reaction —————  52

4.10 Abs Vs time for paracetamol-Zr(IV) reaction————————- 53

4.11   Abs Vs time for paracetamol-V(V) reaction————————- 54

4.12   Effect of temperature on paracetamol-Zr(IV) reaction———— 55

4.13   Effect of temperature on paracetamol-V(V) reaction————- 56

4.14 Beer’s calibration plot for paracetamol- Zr(IV) reaction———– 57

4.15 Beer’s calibration plot for paracetamol – V(V) reaction———– 58

 

 

SCHEMES.

1.3     4-hydroxyacetanilide (paracetamol)——————————— 5

2.6a   Oxidation of paracetamol by cerium(IV)—————————- 23

2.6b   Reaction of paracetamol with KMnO4 in acidic medium——– 27

2.7a   De-acetylation of paracetamol to p-amino phenol—————- 28

2.7b  Oxidation of paracetamol to 2,2-dihydroxy -5,5-diacetyl

diamine biphenyl diamine biphenyl——————————— 29

4.3   Oxidation reaction of paracetamol by Zr(IV)————————- 43

4.5   oxidation reaction of paracetamol by V(V)————————— 48

 

ABSTRACT

           A simple and sensitive spectrophotometric method for the determination of paracetamol was explored, using zirconium(IV) and vanadium(V) oxides. The method was based on the oxidation of paracetamol by zirconium(IV) and vanadium(V) in  alkaline and acidic media respectively. The stoichiometric studies indicated a mole-ratio of 1:1 for the reactions of paracetamol with both zirconium(IV) and vanadium(V). Effects of other variables like pH, temperature and time were determined and showed that the optimum conditions for the oxidation of paracetamol by zr(IV) were pH of 9.0,  temperature of 50˚C and at 20 min yielding red- brown p-benzoquinone which absorbed at a λmax of 420 nm. Similarly, optimum conditions for the oxidation of paracetamol by V(V) were pH of 1.0, temperature of 70˚C at 8 min, and V(V) reduced to bluish-violet vanadium(II) ions which absorbed at a λmax of 600 nm. The Beer-Lambert’s law was obeyed at a concentration range of 5.0-40.0 μg/cm3 for paracetamol with both Zr(IV) and V(V) respectively; and the correlation coefficients for both oxidants were 0.997 and 0.999 respectively. The mean % recovery of paracetamol in dosage form with Zr(IV) was 99.06 %, while V(V) gave 100.17 %. Hence, the recovery studies had proved the method to be accurate, simple and precise.

CHAPTER ONE

1.0    INTRODUCTION

Spectroscopy involves the study of the absorption and emission of light and other radiations as related to wavelength of the radiation. Hence, spectroscopy is the branch of science dealing with the study of interaction between electromagnetic radiation and matter. It is the most powerful tool available for the study of atomic and molecular structures, and is used in the analysis of wide range of samples. Optical spectroscopy includes the region on electromagnetic spectrum between 100 Ǻ and 400 m. Hence, the regions of electromagnetic spectrum are thus – far (or vacuum) ultraviolet (10-200 nm), near ultraviolet (200-400 nm), visible (400 – 750 nm), near infrared (0.75 – 2.2 m), mid infrared (2.5 – 50 m), and far infra red (50 – 100 m) region.2, 3

1.1    Ultraviolet – visible spectrophotometry (UV-visible spectrophotometry).

UV – visible spectrophotometry is one of the most frequently employed techniques in pharmaceutical analysis. It involves measuring the amount of ultraviolet or visible radiations absorbed by a substance in solution.4 Instruments which measure the ratio, or function of ratio, of the intensity of two beams of light in the UV-visible region are called ultraviolet-visible spectrophotometers.4

A spectrophotometer consists of two instruments, a spectrometer and a photometer, both housed in one cabinet. The spectrometer is used to split or resolve light in bands of wavelength before it is fed to the photometer. To achieve the designed resolution, a spectrometer is specially equipped with a high resolution wavelength selector known as monochromatorThis monochromator can isolate an extremely narrow bandwidth almost comparable to a single wavelength.5

In qualitative analysis, organic compounds can be identified by the use of spectrophotometer; if any recorded data is available; and quantitative spectrophotometric analysis is used to ascertain the quantity of molecular species absorbing the radiation.4

Spectrophotometric technique is simple, rapid, moderately specific and applicable to small quantities of compoundsThe fundamental law that governs the quantitative spectophotometric analysis is the Beer-Lambert’s law.

Beer’s Law: it states that the intensity of a beam of parallel monochromatic radiation decreases exponentially with the number of absorbing molecules. In other words, absorbance is proportional to the concentration.

Lambert’s law: It states that the intensity of a beam of parallel monochromatic radiation decreases exponentially as it passes through a medium of homogeneous thickness. A combination of these two laws yields the Beer – Lambert law.4

Beer – Lambert’s Law: When a beam of light is passed through a transparent cell containing a solution of an absorbing substance, reduction of the intensity of light may occur. Mathematically, Beer – Lambert’s law is expressed as –

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