Abstract

Simple and sensitive spectropliotometric methods are described for the assay of three piperazine derivatives ketoconazole, trimetazidine hydrochloride and piribedil based on cliarge-transfer and ion-pair complexation reactions. The first method is based on the reaction of the basic drug with iodine as o-acceptor in dry 1,2-dichloroethane to form a yellow colour due to the formation of charge-transfer complex showing maximum absorbence at 363, 364 and 359 nm for ketoconazole, trimetazidine hydrochlorid and piribedil, respectively. The second method is based on the reaction of basic drug with bromocresol green (BCG) in dry 1,2- dichloroethane to form a stable yellow coloured complex with maximum absorbance at 407, 408 and 410 nm for ketoconazol, trimetazidine hydrochloride and piribedil, respectively. Beer's law was obeyed for both methods and the relative standard deviations were found to be less than 1%. The two methods can be applied for the analysis of tablets and cream, with no evidence of interference from excipients. A more detailed investigation of the complex was made with respect to its composition association constant and free energy cliange.

Highlights

  • Ketoconazole (KC), cis-] -acetyl-4-[4] [2-(2,4-dichloropheny1)-2-(1 H-imidazole-l-ylmethyl)-l,3-dioxolan-4-yl]methoxy]phenyl]piperazine is a highly effective broad spectrum antifungal agent [I]

  • This paper introduces two spectrophotometric methods for the determination of three pharmaceutical piperazine derivatives using iodine (I2) as o-acceptor and bromocresol green (BCG) as chromogenic reagent in 1,2dichloroethane

  • Ketoconazole, piribedil and trimetazidine hydrochloride were of pharmaceutical grade, ketoconazole (Janssen, Beerse, Belgiiiin), piribedil (Eutherapia, France) and trimetazidine hydrochloride (Servier, France)

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Summary

Introduction

Imidazole-l-ylmethyl)-l,3-dioxolan-4-yl]methoxy]phenyl]piperazine is a highly effective broad spectrum antifungal agent [I]. Trimetazidine is determined in tablets using HPTLC [29]. These methods are often time-consuming, expensive and cumbersome. Piribedil (PD), is an alkoxybenzyl-4-(2-pyrimidinyl) piperazine derivative with vasodilatory activity [30]. Methods for the analysis of piribedil or its basic metabolites in biological specimens have used gas chromatography with a nitrogen-sensitive detector [32] or combined with mass spectrometry [33], spectrophotometry [I 3,341, HPLC [35] and ion-selective electrodes [36]. The proposed methods were applied successfully to the determination of ketoconazole, trimetazidine hydrochloride and piribedil either in pure or dosage forms with good accuracy and precision. A Shimadzu UV-1601 spectrophotometer with quartz cells of I -cm optical path length was used

Materials
Reagents
Preparation of standard solutions
Construction of calibration curves
Stoichiometric relationship
Association constant and free energy change
Results and Discussion
Selection of the suitable wavelength
Analytical parameters
Proposed methods
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