DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC METHODS FOR THE DETERMINATION OF RISPERIDONE IN PURE AND TABLET DOSAGE FORMS

DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC METHODS FOR THE DETERMINATION OF RISPERIDONE IN PURE AND TABLET DOSAGE FORMS, A RESEARCH PROJECT TOPIC ON BIOCHEMISTRY

ABSTRACT

Two simple, sensitive, accurate and extraction-free spectrophotometric methods were developed and described for the determination of risperidone in pure and in tablet dosage forms. The methods are based on the formation of ion-pair complex between risperidone and the dyes bromocresol green in method A and thymol blue in method B at room temperature to form yellow coloured products having absorption maxima at 414 nm and 404 nm respectively. The composition of the ion-pairs was established by Job‟s method and it was found to be 1:1 for both methods. Different variables affecting the reaction conditions such as diluting solvents, concentration of dye, reaction time were studied and optimized. Under the optimal conditions, linear relationship with good correlation coefficients (0.994 and 0.995 for methods A and B respectively) was found between absorbance and the concentrations of risperidone in the range of 2-20 µg/ml and 20-40 µg/ml respectively. The assay limits of detection (LOD) and limits of quantification (LOQ) were 1.27 and 3.84 µg/ml for method A and 7.00 and 21.15 µg/ml for method B. The precision of both methods did not exceed 15% likewise the percentage relative error was within the accepted range of 1-5%. No interference could be observed from the excipients commonly present in tablet or liquid dosage forms. The methods developed have been validated and there is no significant difference (P < 0.05) between the methods and the reference (BP) method. The methods can be successfully applied for the analysis of risperidone in pure and tablet dosage forms.

CHAPTER ONE

1.0 INTRODUCTION

1.1 Preamble

Risperidone is a psychotropic (antipsychotic) agent used in the treatment of schizophrenia. The action is mediated through a combination of dopamine Type 2 (D₂) and serotonin Type 2 (5HT₂) receptor antagonism. It is a selective monoaminergic antagonist with high affinity for 5HT₂, D₂ and H₁histaminergic receptors (Potter and Hollister, 2001). It belongs to the chemical class of benzisoxazole derivatives. The chemical name of risperidone is 3-[2-[4-(6-fluoro-1, 2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6, 7, 8, 9-tetrahydro-2-methyl-4H-pyrido-[1,2-a]-pyrimidin-4-one) while the molecular formula is C₂₃H₂₇FN₄O₂ with the molecular weight of 410.49g (The Merck Index, 2001).

DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC METHODS FOR THE DETERMINATION OF RISPERIDONE IN PURE AND TABLET DOSAGE FORMS, A RESEARCH PROJECT TOPIC ON BIOCHEMISTRY