Voltammetric Determination of Ethionamide in Pharmaceutical Formulations and Human Urine using a Boron-Doped Diamond Electrode

Bruno R L Ferraz,Fernando R F Leite,Bruna L Batista,Andréa R Malagutti

doi:10.5935/0103-5053.20150313

Bruno R L Ferraz, Fernando R F Leite + Show 2 more

Open Access

https://doi.org/10.5935/0103-5053.20150313

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Abstract

This work reports a simple and low cost voltammetric approach comprising a boron-doped diamond electrode (BDDE) to determine the antibiotic ethionamide (ETO). Cyclic voltammetry studies revealed that ETO exhibits an irreversible reduction peak at -0.95 V and an irreversible oxidation peak at +1.4 V onto BDDE (vs. saturated Ag/AgCl reference electrode) in Britton-Robinson buffer solution (pH 5.0, 0.1 mol L-1). Different voltammetric scan rates (from 10 to 150 mV s-1) suggested that the reduction of ETO on the BDDE surface is a diffusion-controlled process. Square wave voltammetry (SWV) optimized conditions showed a linear response to ETO from 1.00 to 80.0 µmol L-1 (R2 = 0.998) with a limit of detection of 0.294 µmol L-1 and limit of quantification of 0.980 µmol L-1. The developed square wave voltammetric method was successfully used in the determination of ETO in human urine and pharmaceutical formulation. The ETO quantification results in pharmaceutical tablets obtained by SWV-BDDE were comparable to those found by official analytical protocols.

Highlights

Ethionamide (ETO, 2-ethylpyridine-4-carbothiamide; Figure 1) is an oral bacteriostatic antibiotic used for treatment of tuberculosis (TB).[1]
The development of a reproducible, sensitive and reliable analytical method to determine ETO in biological fluids and pharmaceutical formulations has been crucial to monitor the efficacy of the MDR-TB treatment and to ascertain whether a drug has the proper content of active substance
This work demonstrated that a Square wave voltammetry (SWV)-boron-doped diamond electrode (BDDE) method can be used to quantify ETO in human urine and pharmaceutical formulations

Summary

Introduction

Ethionamide (ETO, 2-ethylpyridine-4-carbothiamide; Figure 1) is an oral bacteriostatic antibiotic used for treatment of tuberculosis (TB).[1] It has been an important second line drug in the therapy of drug-resistance tuberculosis (MDR-TB) caused by Mycobacterium tuberculosis, which has become resistant to the first line anti-tuberculosis drugs, such as isoniazid and rifampicin.[2,3] ETO is almost fully metabolized by the liver, being only approximately 5% of the antibiotic excreted in an unaltered form in the urine.[4] the minimum dose of ETO to inhibit the growth of M. tuberculosis is sufficiently high to cause grave side effects, including gastrointestinal disorders, hepatotoxicity, neurotoxicity, cardiovascular effects, endocrine effects and skin reactions.[4] The duration of the treatment of MDR-TB is usually from two to four years, and requires the use of second-line drugs that are less effective and often poorly tolerated, especially by patients with a weakened immune system, leading to high recurrence rates and mortality.[3]. Some analytical methodologies, such as spectrophotometry,[5,6] fluorimetry[7,8] and high-performance liquid chromatography (HPLC)[9,10,11,12,13] have been applied to quantify ETO in pharmaceutical formulations and body fluids or tissues after its intake

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