Determination of theophylline and ephedrine HCL in tablets by ratio-spectra derivative spectrophotometry and LC

Abstract

Two methods are described for the determination of theophylline (THP) and ephedrine hydrochloride (EPH) in combined pharmaceutical tablet forms. The first method depends on the use of the first derivative of the ratio-spectra obtained by dividing the absorption spectrum of binary mixtures by a standard spectrum of one of the compounds. The first derivative amplitudes at 231.8 and 250.3 nm were selected for the assay of THP and EPH, respectively. Calibration graphs were established for 20–180 μg ml⁻¹ for THP and 10–50 μg ml⁻¹ for EPH. The second method is based on high-performance liquid chromatography on a reversed-phase column using a mobile phase of methanol–water (40+60,v/v) (pH 3) with detection at 217 nm. Linearity was obtained in the concentration range of 5–150 μg ml⁻¹ for THP and 15–75 μg ml⁻¹ for EPH. The detection limits for THP and EPH were 0.73 and 0.92 μg ml⁻¹ by ratio-spectra derivative spectrophotometry and 0.59 and 0.86 μg ml⁻¹ by HPLC, respectively. The proposed methods were successfully applied to the determination of these drugs in laboratory-prepared mixtures and in tablets. The relative standard deviations were found to be less than 1.5%, indicating reasonable repeatibility of both methods.

Introduction

Theophylline (THP), a member of xanthine-based alkaloids, which relaxes smooth muscles and relieves broncospasm, has a stimulant effect on respiration. Ephedrine hydrochloride (EPH), a sympathomimetic agent, is used as an expectoran. The association of these drugs might produce a synergy effect in the therapy. THP has been marketed in combination with EPH in pharmaceutical formulations for being used in the symptomatic treatment of bronchial asthma and other bronchospastic conditions [1], [2].

Several methods have been described for the quantitative determination of THP and EPH in dosage forms containing these drugs either alone or in combination with other active ingredients, including high-performance liquid chromatography [3], [4], [5], [6], [7], [8], [9], [10], gas chromatography [11], [12], [13], [14], micellar electrokinetic capillary chromatography [9], [15], [16], high-performance thin layer chromatography [17], [18], densitometry [19], potentiometry using ion-selective membran electrode [20], [21], [22], and spectropotometry [4], [23], [24], [25], [26], [27], [28], [29].

Although many methods exist for the assays of both drugs as seen above, only a few procedures deal with the determination THP and EPH in presence of each other. Most of them, which include liquid chromatography [30], [31], CPA-matrix UV-spectrophotometry [32], capillary electrophoresis [33], involve the assay of both drugs in multicomponent mixtures with other drugs, such as phenobarbital, amobarbital, papaverine and hydroxyzine. Recently, differential-derivative spectrophotometry has been published, which allows specifically the determination of THP and EPH together in their dosage forms [34]. Pharmacopoeial method involves the HPLC determination of both drugs, including conbination with phenobarbital in tablets [35].

One of the classic analytical problem of spectrophotometric multicomponent analysis is that the analyte of interest is often accompanied by other compounds absorbing in the same spectral region. Under computer-controlled instrumentation, derivative spectrophotometry are playing a very important role in the resolution of band overlapping in quantitative analysis. However, for binary mixtures, the classical zero-crossing method requires often to use a wavelength with low sensitivity in the measurements. Salinas et al. [36] designed a new spectrophotometric method, which is based on the derivation of the ratio-spectra for resolving binary mixtures. The main advantage of the ratio-spectra derivative spectrophotometry is the chance of doing easy measurements in correspondence of peaks so it permits the use of the wavelength of highest value of analytical signals (a maximum or a minimum) [37], [38], [39]. Moreover, the presence of a lot of maxima and minima is another advantage by the fact that these wavelengths give an opportunity for the determination of active compounds in the presence of other compounds and excipients which possibly interfere the assay.

The present work is a continuation of the authors’ research [40], [41], [42], [43], [44] on the possibility of the application of ratio-spectra derivative spectrophotometry in the analysis of multi-component systems, allowing an increase in the selectivity of spectrophotometric determination. This ratio-spectra derivative method has been applied to the determination of THP and EPH in both pure forms and pharmaceutical tablets. As a comparison method, a reversed-phase high performance liquid chromatography (RP-HPLC) has also been developed since chromatographic techniques have been mainly used for the analysis of multicomponent mixtures in pharmaceutical preparations reported in pharmacopoeias.