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.

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