Ethambutol analysis by copper complexation in pharmaceutical formulations: spectrophotometry and crystal structure

Abstract

Um método alternativo para determinação de etambutol (ETB) por espectrofotometria UV em formulações farmacêuticas por complexação com Cu(II) foi otimizado usando um planejamento fatorial completo 3 2 , tendo como variáveis Cu(II) e tampão aquoso de acetato de sódio em pH 4,6. A estequiometria predominante do complexo em solução aquosa tamponada nesse pH e a constante de formação do complexo foram obtidas usando o método de Job e o diagrama de Scatchard, respectivamente. A estrutura cristalina do complexo de monocristal foi obtida por difração de raios X. O método espectrofotométrico foi aplicado na análise de formulação farmacêutica sendo encontrado: 408,0 ± 11,9 mg de ETB•2HCl, faixa de recuperação de 100,9-104,0% e limites de detecção e quantificação de 0,8 e 2,8 mg L -1 , respectivamente. O método espectrofotométrico ao ser comparado com o método por eletroforese capilar de zona não evidenciou diferenças significativas no intervalo de 95% de confiança.An alternative method for ethambutol (ETB) determination by UV spectrophotometry in pharmaceutical formulations using ETB complexation with Cu(II) was optimized employing a 3 2 full experimental design having Cu(II) and aqueous acetic acid/sodium acetate buffer at pH 4.6 as variables. The predominant complex stoichiometry in aqueous buffer solution at this pH and formation constant were obtained by using Job's method and Scatchard diagram, respectively. The complex crystalline structure of monocrystal was obtained by X-ray diffraction. The developed method was applied to the pharmaceutical formulation analysis being found: 408.0 ± 11.9 mg of ETB•2HCl, recovery range of 100.9-104.0% and detection and quantification limits of 0.8 and 2.8 mg L -1 , respectively. The spectrophotometric method was compared to zone capillary electrophoresis and no significant difference was found within the 95% confidence interval.Keywords: ethambutol, complexation, spectrophotometry, crystal structure IntroductionNowadays, tuberculosis (TB) is becoming a worldwide problem. This contagious disease is transmitted through the air and it is caused by the bacterium Mycobacterium tuberculosis, which can attack different organs of the human body. However, it most commonly affects the lungs, accounting for more than 75% of the cases.1 According to the World Health Organization (WHO), more than two billion people are infected with TB bacilli and a total of 1.77 million people died from TB in 2007.2 Nowadays, the first line TB treatment is based on four drugs: isoniazid, rifampicin, pyrazinamide and ethambutol (ETB), which are available in cheap generic forms and are effective if taken as prescribed. 3 These drugs complement each other and are used in various combinations, which are very important to prevent the emergence of multiple drugresistant organisms, resulting in ineffective treatment. 3In this context, ETB is an important component in TB treatment (Figure 1). This drug is an aminoalcohol, which affects the biosynthesis of mycolic acids, an important class of compounds frequently found...

Preparation and characterisation of ethambutol with β-cyclodextrin: a comprehensive molecular insight into host-guest interaction

“…The extent of interaction involved for the inclusion complex formation was determined by observing the changes in UV–Vis absorbance. However, direct ETB determination in UV–Vis range is not feasible due to its low molar absorptivity in aqueous form [ 8 ]. Hence, complexation of ETB with Cu(II) was carried out as developed by Faria et al (2011).…”

Modular Titratable Polypills for Personalized Medicine and Simplification of Complex Medication Regimens

“…Ethambutol analyses were adapted from a quantitative spectrophotometric method using complexation with copper (II). [ 34 ] HPLC was performed using an Agilent Poroshell 120 EC‐C18 column (3.0 × 50 mm, 2.7 µm) held at 25 °C. A mobile phase of 1 m m copper (II) sulfate and 10 m m ammonium formate adjusted to pH 4.6 with ammonia (A) and methanol (B) was used.…”

Reducing the Hygroscopicity of the Anti-Tuberculosis Drug (S,S)-Ethambutol Using Multicomponent Crystal Forms

“…In order to overcome the undesirable effects of ( S , S )-EDH, an extensive amount of studies have been emerged in the last few years, many of them dealing with the development of multicomponent crystal forms of this drug. − Recently, Nangia et al have been prepared and characterized five salts (sulfate, dimesylate, ditosylate, dibesylate, and fumarate) and two ionic liquids (dibenzoate and adipate), but all of them were found to be hygroscopic . For this reason, herein we report a screen of ETB with a series of carboxylic/dicarboxylic acids, trichloroacetic, maleic, oxalic, and terephthalic acids.…”