Amplified anodic electrogenerated chemiluminescence of tris(2,2′-bipyridyl)ruthenium(II) for ultrasensitive detection of bambuterol: Application to content uniformity testing

https://doi.org/10.1016/j.jelechem.2020.114881Get rights and content

Highlights

  • BAM was introduced for the first time an intense ECL coreactant for Ru(bpy)32+ luminophore.

  • Ru(bpy)32+-BAM was used for BAM detection in its pure form and tablets.

  • The developed method was utilized to determine the content uniformity of BAM in low dose tablets.

Abstract

Asthma is one of the most common chronic diseases among children and has affected about 300 million individuals worldwide according to the report of the world health organization. Herein, we present the first electrochemiluminescence (ECL) report for the determination of an important antiasthmatic drug (Bambuterol). It was found that bambuterol can act as an efficient coreactant for Ru(bpy)32+ ECL via oxidation-reduction pathway. The electrogenerated reducing species from bambuterol and Ru(bpy)32+ could react together at the surface of gold electrode to generate an intense ECL signal. Based on this new finding, the first ECL study was proposed and optimized for the rapid, highly sensitive, and selective screening of bambuterol in its pure form with a wide linearity of 10.0 nM - 2.0 μM and an ultra-low detection limit of 1.48 nM. The developed system was applied for assaying bambuterol in pharmaceutical preparations. Furthermore, the developed system was also utilized to determine the content uniformity of bambuterol in low dose tablets.

Introduction

Electrochemiluminescence (ECL) that combines the features of both electrochemistry and photoluminescence is a highly promising technique for the determination of diverse samples in different complicated matrices as plasma and urine with ultra-selectivity and sensitivity [[1], [2], [3]]. Ru(bpy)32+ ECL is widely applicable in many application (biologically and environmentally) rather than other luminophores [4,5]. Ru(bpy)32+ ECL has been utilized pharmaceutically for the detection of different pharmaceutical active ingredients such as antibiotics and antidepressants drugs [[6], [7], [8]]. Specifically, anodic ECL of Ru(bpy)32+ has undergone a huge advancement in many important fields for humans as clinical investigations, environmental analysis, food and drug monitoring [9]. In such systems, ECL intensity could be enhanced by using coreactants for Ru(bpy)32+ [[10], [11], [12]]. Coreactant ECL shows superiority than annihilation ECL in analytical applications due to the single potential sweep, using aqueous buffered solutions (environmentally friendly), and the radical species are generated at lower potentials than organic solvents [13].

Bambuterol hydrochloride (BAM) (Fig. 1) is an important drug that is used as the first line of treatment for asthma. It is an ester prodrug of terbutaline (TER). It has an affinity for lung tissue, a relative stability to pre-systemic metabolism, and a relative specificity for hydrolysis by butyryl-cholinesterase enzyme (liberating TER) [14]. Given once daily, BAM controls the symptoms in asthmatic patients with lower side effects than those produced from TER given twice or three times daily [15]. Antiasthmatic effect of BAM was attributed to its sympathomimetic and B2 agonistic action. Also, BAM has a long acting bronchodilator effect which plays a vital role in the treatment of asthma [16]. Though different analytical methods such as spectroscopic [[17], [18], [19], [20], [21], [22], [23], [24]], chromatographic [[25], [26], [27], [28], [29], [30], [31]] and electrophoretic methods [32] have been reported for the detection of BAM, most of these methods involve complicated analytical procedures, highly expensive instrumentation and analysis, and harmful reagents used in the extraction procedures. Moreover, most of the electrochemical sensors for BAM detection used complicated synthetic procedures for fabrication of different nanomaterials for modification of the surface of the electrodes [33,34]. In contrast, ECL technique is simple and sensitive in a wide dynamic range. In addition, it is considered a green chemistry as most of ECL reports didn't used organic solvents. In this report we have used the features of ECL technique for the determination of BAM in its pure form and its tablets dosage form. BAM could act as a stable and efficient coreactant for Ru(bpy)32+. To our knowledge it is the first ECL report for determination of BAM. The new ECL system exhibits high sensitivity and high specificity for BAM detection in tablet dosage form (Scheme 1). Additionally, the developed ECL method is fast, facile, easily operated and highly sensitive in comparison with reported methods (Table S1). Furthermore, the developed ECL system was used to establish the content uniformity testing of BAM in its tablets.

Section snippets

Chemicals and reagents

BAM powder (98.79%) was kindly provided by multiapex pharma Company, Badr city – Cairo. Bambec tablets were purchased from a pharmacy in Egypt. Ru(bpy)3Cl2·6H2O, luminophore was obtained from Sigma Aldrich. Phosphate buffer solution (PBS) with various pH values was formed by mixing appropriate volumes from Na2HPO4 and Na3PO4 solutions.

Instrumentation

Shanghai CHI Instruments Company, located in China provided us a CHI 660C electrochemistry workstation for recording the cyclic voltammetric measurements using

Electrochemistry and ECL of Ru(bpy)32+/BAM system

Ru(bpy)32+ and BAM solutions were tested by cyclic voltammetry to check their electrochemical behaviors (see Fig. 2A). A reversible characteristic peak for the redox reaction of Ru(bpy)32+/3+ was obtained at about 1.1 V (Au vs Ag/AgCl) in the absence of BAM. Surprisingly, the presence of BAM makes a little enhancement in the current of the oxidation peak of Ru(bpy)32+ and a slight quenching effect on reductive current. These results clearly indicate to the electrocatalytic oxidation of BAM by

Linearity, LOD and LOQ

Fig. 5 exhibits the constructed calibration plot for BAM detection based on Ru(bpy)32+ luminophore. Using amperometric conditions, ECL signal intensity and BAM concentrations was directly proportional to each other with a good linearity (R2 = 0.999) from 10 nM to 2.0 μM. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 1.48 nM and 5.0 nM, respectively. Based on ICH recommendations [39], validation parameters for example linearity, LOD and LOQ were calculated using

Analysis of tablets and comparison with the reference spectrofluorimetric method

Bambec® tablets containing BAM active ingredient was tested using the new ECL system and the reference method [22] as well. The average percentage recovery for the assay of the tablets was 100.04 ± 1.34 as listed in Table 1. The results obtained from the developed ECL system and those of the reference method were statistically compared using t- and F- tests at 95% confidence interval. The calculated values of t and F are lower than the tabulated values; this indicates there is no significant

Conclusion

In this work, we reported BAM as an efficient stable coreactant for Ru(bpy)3 2+ ECL without the addition of any catalysts for the first time. The developed ECL system permits the detection of Ru(bpy)3 2+ and BAM (in its pure powder form and tablets dosage form) with good sensitivity and reproducibility. Furthermore, the content uniformity testing of BAM in its Bambec® tablets was investigated by the developed ECL method with average percentage recovery of 99.31 ± 0.98%. The new ECL system has

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

This work was supported by the National Nature Science Foundation of China (21574085), the Natural Science Foundation of Guangdong Province (2016A030312002, and 2017A030313067) and Faculty of Pharmacy, Mansoura University, Egypt.

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