Elsevier

Diamond and Related Materials

Volume 82, February 2018, Pages 109-114
Diamond and Related Materials

Study of electrooxidation and enhanced voltammetric determination of β-blocker pindolol using a boron-doped diamond electrode

https://doi.org/10.1016/j.diamond.2018.01.010Get rights and content

Highlights

  • Pindolol (PND) is determined by voltammetric method.

  • A cathodically pretreated BDD electrode was used as working electrode.

  • This method can be used to control PND in anti-doping diagnoses.

  • The SWV method is applied in pharmaceutical and urine analysis.

  • The attained LOD is the lowest ever attained by an electroanalytical method.

Abstract

Pindolol (PND), an antihypertensive agent indicated for patients in the treatment of angina, hypertension, cardiac arrhythmias and recently consumed as doping agent by athletes, is electrochemically determined in this research by using a cathodically pretreated boron-doped diamond (CPT-BDD) electrode. The electrochemical response of PND studied via cyclic voltammetry on the BDD surface, shows an irreversible oxidation process. From cyclic voltammetric assays carried out at different potential scan rates, the electrochemical parameters number of electrons transferred and the apparent heterogeneous electron transfer rate constant (k0app) were determined. Additionally, chronoamperometric measurements performed at different PND concentration levels yielded the apparent diffusion coefficient of this molecule (Dapp) in 0.2 mol L−1 phosphate buffer solution (pH = 6.0). After a number of optimization steps, a differential pulse voltammetric (DPV) procedure for the sensitive determination of PND using the CPT-BDD electrode was developed. Under the optimum experimental conditions, the obtained analytical curve was linear in the wide concentration range from 0.04 to 10.0 μmol L−1 and a limit of detection of 26 nmol L−1 was also determined. The viability of the proposed voltammetric procedure was checked out towards the quantification of PND in pharmaceutical formulation samples and biological fluids. The successfully application of the proposed voltammetric procedure suggest the potentiality of this approach for field applications, such as control of pharmaceutics and monitoring of PND in biological samples from athletes subjected to anti-doping exams.

Introduction

Pindolol (PND) is an antihypertensive agent indicated for patients in the treatment of angina, hypertension and cardiac arrhythmias; including pregnant women, because it is not teratogenic [1, 2]. Furthermore, this drug recently have been used as doping agent by athletes, particularly in sports in which good psychomotor coordination is required; due to this, PND is in the list of prohibited substances in particular sports, published by the World Anti-Doping Agency [3, 4].

PND belongs to the group of non-selective beta-adrenergic antagonists (beta-blockers), which acts to affect the response to certain nerve impulses, in certain parts of the body, for example: the heart, blood vessels and bronchi, and reduces blood pressure [5, 6]. When ingested, PND is rapidly absorbed; its metabolism occurs in the kidney and liver, being excreted in the urine in an amount of 35–40% of the dose consumed in its unchanged form, as well as in the form of inactive metabolites (60–75%) [6, 7].

Drug analysis in biological systems provides valuable information for pharmacokinetic studies, clinical diagnosis, in cases of intoxication and also in the doping control in world sport. Thus, the sensitive determination of PND in biological fluids and pharmaceutical samples (for quality control) is required. In this sense, electroanalytical methods appear as promising alternatives to more classical approaches, because requires a short-time of analysis and low consumption of reagents, besides generally do not require steps of pre-treatment and extraction of the sample.

The PND is an electroactive substance and, thus, it can be oxidized electrochemically, as reported in the literature [[8], [9], [10]]. Smarzewska and Ciesielski, studied the electrochemical oxidation of PND at a glassy carbon electrode (GCE) modified with reduced graphene oxide (RGO). They observed that in BR buffer (pH 5.0) medium the oxidation process involves the transfer of two electrons and two protons, generating the oxidized specie oxipindolol [8]. So far, studies found in the literature regarding the PND eletrooxidation are based on modified electrodes whose preparation demands > 1 h, in addition to special care to ensure reproduction in the preparation [[8], [9], [10]].

In this aspect, the boron-doped diamond (BDD) electrode is an excellent alternative to modified electrodes, because it requires only a simple electrochemical pretreatment at the beginning of every work day, a procedure that takes <5 min. Furthermore the BDD electrode presents attractive electrochemical properties, such as low and stable background current, wide potential window, low adsorption, and long-term stability of the response [11]. These properties of BDD electrode are extremely affected by their surface termination (oxygen or hydrogen), which can be modified by a proper electrochemical pretreatment (cathodic or anodic pretreatment, leading to hydrogen-termination or oxygen-termination enrichment of the electrode surface, respectively) [12, 13].

Thus, in this paper we describe the electrochemistry study of PND and the development of a method for its voltammetric determination in pharmaceutic and biological fluid samples using a cathodically pretreated BDD electrode.

Section snippets

Reagents, solutions and samples

Standard of PND (purity ≥ 98%) was purchased from Sigma-Aldrich. All reagents at least of analytical grade were used and ultra-pure water with resistivity > 18 MΩ cm from a Gehaka MS 2000 system was employed for preparation of aqueous solutions. Stock standard solution of PND (1.0 × 10−2 mol L−1) was daily prepared in 0.1 mol L−1 HCl. The supporting electrolyte was a 0.2 mol L−1 phosphate buffer solution (pH 6.0). Pharmaceutical tablet samples were acquired in a local drugstore. The synthetic

Electrochemical response of PND

Using cyclic voltammetry, the electroactivity of PND compound on BDD electrode was investigated. In the initial studies a 0.2 mol L−1 phosphate buffer solution (pH = 6.0) was used as supporting electrolyte and an analyte concentration of 5.0 × 10−4 mol L−1. Fig. 1 reports the cyclic voltammograms recorded on these conditions in the potential window from +0.4 V to +1.0 V using as working electrode a CPT-BDD or an APT-BDD. For both electrodes, an oxidation peak was observed during the anodic

Conclusions

The electrochemical response of PND was investigated on the surface of a cathodically pretreated BDD electrode and a differential pulse voltammetric electroanalytical procedure optimized in this work. Different electrochemical features of the irreversible PND oxidation were determined, including number of electrons transferred, apparent heterogeneous electron transfer rate constant and apparent diffusion coefficient. Then, a wide linear concentration range from 0.04 to 10.0 μmol L−1 and a limit

Acknowledgments

We gratefully acknowledge the Brazilian agencies FAPITEC, CAPES (grant: 2328/2012), CNPq (grants: 310282/2013-6 and 444150/2014-5) and PROBIC/UNIT for their financial support. P. B. Deroco is particularly grateful to the São Paulo Research Foundation (FAPESP) for the award of a doctorate scholarship (grant no. 2014/07919-2).

References (31)

  • S.A. Qasqas et al.

    Cardiovascular pharmacotherapeutic considerations during pregnancy and lactation

    Cardiol. Rev.

    (2004)
  • P. Kintz et al.

    Doping control for β-adrenergic compounds through hair analysis

    J. Forensic Sci.

    (2000)
  • World Anti-Doping Agency

    The world anti-doping code, prohibited list January 2018

  • W. Klykylo et al.

    Green's Child and Adolescent Clinical Psychopharmacology

    (2007)
  • U. S. Food and Drug Administration

    Visken®

  • Cited by (19)

    • Developed electrochemical sensors for the determination of beta-blockers: A comprehensive review

      2021, Journal of Electroanalytical Chemistry
      Citation Excerpt :

      Consequently, BDDE has been widely used for the voltammetric quantification of various analytes especially the ones that has a very positive oxidation peak potential. Owing to the fact that most of the β-blockers have a too positive potential peak in the anodic region near the end boundary of the solvent potential window, it seems BDDEs can be a promising working electrode for their anodic voltammetric determination (Table 5) [142–148]. The first BDDE based sensor for the quantification of β-blockers was reported by Sartori et al. in 2010 for the simultaneous SWV determination of Atenolol and propranolol in tablet samples by a cathodically pre-treated BDDE [148].

    • Development of a simple and rapid screening method for the detection of 1-(3-chlorophenyl)piperazine in forensic samples

      2021, Talanta
      Citation Excerpt :

      In forensic analysis, the development of simple and portable methods is highly desirable to overcome some limitations of conventional approaches used in preliminary identification tests of illicit drugs [7,26]. In this context, electrochemical techniques can be a powerful alternative for point-of-care analysis due to their properties, such as low-cost, simplicity, requires a short-time of analysis with minimal facilities or even outside the lab (use of battery powered equipment) [26–32]. Due to these properties, electroanalytical techniques are being exploited for determination of mCPP and other piperazines in several types of samples [17,33–35], as well as for other illicit drugs [29,33,36–38].

    • Recent progress in the applications of boron doped diamond electrodes in electroanalysis of organic compounds and biomolecules – A review

      2019, Analytica Chimica Acta
      Citation Excerpt :

      As a result, it can be used for samples with limited number of electrochemically active components. Nevertheless, this condition is often fulfilled in pharmaceutical preparations [259–262], less complex food matrices [105,120] or even in biological matrices such as blood serum, particularly if the concentration of the analyte is high enough [263]. Several works further increase the selectivity by generator/collector principle – oxidation products of the reaction occurring during the first pulse are determined during the subsequent pulse.

    View all citing articles on Scopus
    View full text