Electrochemical sensor for determination of desipramine in biological material

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Abstract

A simple electrochemical method for determination of desipramine in human oral fluid was developed. Two types of electrodes, namely: glassy carbon electrode (GCE) and screen-printed electrode (SPE) were tested with different electrochemical techniques: cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The simplex method was applied to find optimal instrumental conditions of DPV measurements. Three parameters were subjected to optimization with the simplex method procedure, namely: potential of the pulse (Ep), potential difference between pulses (Es) and pulse time (tp). Buffer solution pH and material of the working electrode were tested in a pre-optimization step. For optimal working conditions of a given screen-printed electrode two ranges of desipramine concentration were tested. Signals registered for desipramine within the range of 0.01–1 μM enabled its determination in alternative biological material such as oral fluid.

Introduction

Tricyclic antidepressant drugs (TCAs) such as: amitryptyline, doxepin, imipramine and their metabolites: nortryptyline, nordoxepin and desipramine, respectively, are still used in the treatment of depression. The function of these substances is to block reuptake of the neurotransmitters: serotonin and norephinephrine in the central nervous system [1]. Apart from its therapeutic effect it may cause negative side effects such as: convulsions, parasthesia, hallucinations, delusions, tachycardia or arythmia [2]. Therefore, choosing the proper therapeutic dose is one of the most important elements of a treatment. In particular, the therapeutic range for desipramine lies between 115 and 250 ng mL−1, whereas the toxic dose starts above 500 ng mL−1 and plasma half-life is 12–28 h [3]. Consequently, possibility of determination of desipramine and other psychoactive drugs in biological material, especially in field conditions, becomes a necessary element of drug abuse control along with inspection of drivers and employees on their workplace.

Among various methods of desipramine determination gas and liquid chromatography remain the most popular [2], [4], [5], [6], [7]. Electroanalytical methods, despite being much cheaper and very useful in field conditions, require electroactivity of a given compound. While most tricyclic drugs are electrochemically inactive, imipramine and its metabolite – desipramine (DMI) can be easily oxidized in a two-step two-electron mechanism [8]. Wang et al. [1] proposed determination of tricyclic antidepressant drugs with the use of glassy carbon electrode and carbon paste electrode. Potentiometric and amperometric measurements with the use of alkylated cyclodextrin-based electrodes were presented by Katak et al. [9]. Application of highly boron-doped diamond electrodes coupled with HPLC enabled determination of tricyclic antidepressant drugs within a wide linear range with limits of detection at the level of nM [10]. Hyphenation of micellar liquid chromatography with electrochemical detection at the potential of 650 mV allowed for determination of imipramine and its metabolite directly in blood samples [11]. Galeano-Díaz et al. evaluated a method for simultaneous determination of imipramine and desipramine on a glassy carbon electrode with the use of adsorptive stripping voltammetry with PLS-1 multivariate calibration method [12].

Growing popularity of saliva as an alternative material for clinical analyses, observed in the recent years, results from the benefits of the afore-mentioned biological material. Popularity of oral fluid (OF) arises from the fact that material collection is non-invasive, may be done in any place and does not require qualified personnel [13], [14], [15]. Oral fluid is a complex biological matrix which consist of products of salivary glands mixed with other fluids, substances, dead epithelial cells, food leftovers present in the oral cavity. Water stands for 99% of saliva, whereas organic compounds (mainly enzymatic proteins) make as little as 0.3%. The rest are inorganic compounds, mainly ions [16]. Among the pathways of drug incorporation into saliva, the most important role is played by passive diffusion across the concentration gradient through lipid membranes, the rest being active transport and ultrafiltration [17]. Low protein content in saliva allows for analysis of free fraction of drugs. Depending on pKa value of a given xenobiotic along with pH of the oral fluid, saliva/plasma ration is usually below 1 for basic drugs [18].

As a process of searching for the best solution to a problem, in relation to a given criterion, optimization plays a crucial role in chemical analysis. Among various optimization methods the simplex method, and especially its modification proposed by Nelder and Mead [19], [20], deserves special attention due to simplicity and rapidity in giving solution to a problem. Optimization of experimental conditions leads to more repeatable and more accurate results, gives an opportunity to improve sensitivity of the method of interest and consequently to lower both detection and quantification limit.

The aim of this paper is to draw attention to importance of optimization of experimental conditions as well as presentation of the possibility of desipramine determination in alternative biological material.

Section snippets

Materials and method

Desipramine (Sigma, ≥98%), potassium dihydrogen phosphate (Aldrich, 99.99%), dipotassium phosphate (Fluka, ≥99%), potassium chloride (Sigma–Aldrich, ≥99.5%), hydrochloric acid 35% (Sigma–Aldrich), potassium hydroxide (Sigma–Aldrich) were used as purchased. Distilled and deionized water was used in preparation of all solutions and during all measurements. All solutions were purged with nitrogen before use.

Instrumentation

PalmSens Instrument (Palm Instrument BV, Holland) was applied in all measurements of

Preliminary experiments

Oxidation of both desipramine and imipramine is limited by the material of the employed working electrode. Several types of working electrodes were tested, namely: gold, platinum, glassy carbon and graphite paste electrode and the latter two were selected for further study. Gold and platinum electrodes did not allow to register signal in the studied concentration range – it was much more difficult to oxidize desipramine and imipramine on these electrodes than on carbon electrodes.

Phosphoric

Conclusion

The proposed sensor is characterized with wide response linearity range (0.01–1 μM), detection limit of 0.007 μM for desipramine and sensitivity of 3.004 and 3.200 nA nM−1 for the small- and large-volume cell, respectively. Influence of some experimental parameters, such as buffer composition, buffer pH, surface of working electrode, was evaluated in a preliminary study. Simultaneously it was proven that pH of the employed phosphorus buffer strongly influenced the obtained results, and necessity of

Acknowledgements

The research was financed by the Polish Ministry of Science and Higher Education from the European Union Structural Funds (European Regional Development Funds), project MNS-DIAG: POIG.01.03.01-00-014/08-02. We thank Magdalena Kruszewska and Marianna Bienias for their excellent technical assistance in the performed research.

Paweł Knihnicki received his master degree (M.Sc.) in Chemistry from the Jagiellonian University in 2008 and his engineer degree (Eng) in Chemical Technology from the AGH University of Science and Technology in 2011. Currently, he is a Ph.D. student in the Department of Analytical Chemistry at the Jagiellonian University in Cracow under the supervision of Prof. Paweł Kościelniak. His research activity is mainly focused on development of advanced electroanalytical methods for determination of

References (21)

  • A. de Castro et al.

    LC–MS/MS method for determination of nine antidepressants and some of their metabolites in oral fluid and plasma. Study of correlation between venlafaxine concentrations in both matrices

    Journal of Pharmaceutical and Biomedical Analysis

    (2008)
  • S. Chiappin et al.

    Saliva specimen: a new laboratory tool for diagnostic and basic investigation

    Clinica Chimica Acta

    (2007)
  • J. Wang et al.

    Voltametric measurements of tricyclic antidepressants following interfacial accumulation at carbon electrodes

    Analytical Chemistry

    (1986)
  • K. Madej et al.

    Review of analytical methods for identification and determination of PHEs and tricyclic antidepressants

    Critical Reviews in Analytical Chemistry

    (2008)
  • M.W. Linder et al.

    Standards of laboratory practice: antidepressant drug monitoring

    Clinical Chemistry

    (1998)
  • S. Rana et al.

    A new method for simultaneous determination of cyclic antidepressants and their metabolites in urine using enzymatic hydrolysis and fast GC–MS

    Journal of Analytical Toxicology

    (2008)
  • C. Coulter et al.

    Antidepressant drugs in oral fluid using liquid chromatography–tandem mass spectrometry

    Journal of Analytical Toxicology

    (2010)
  • L. Hu et al.

    Simultaneous determination of six analytes by HPLC–UV for high throughput analysis in permeability assessment

    Journal of Chromatographic Science

    (2011)
  • M. Woźniakiewicz et al.

    Determination of desipramine and nortriptyline in blood by means of the HPLC-DAD method using 7,7,8,8-tetracyanoquinodimethane (TCNQ) as a derivatisation agent

    Problems of Forensic Science

    (2007)
  • E. Bishop et al.

    Electroanalytical study of tricylic antidepressant

    Analyst

    (1984)
There are more references available in the full text version of this article.

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Paweł Knihnicki received his master degree (M.Sc.) in Chemistry from the Jagiellonian University in 2008 and his engineer degree (Eng) in Chemical Technology from the AGH University of Science and Technology in 2011. Currently, he is a Ph.D. student in the Department of Analytical Chemistry at the Jagiellonian University in Cracow under the supervision of Prof. Paweł Kościelniak. His research activity is mainly focused on development of advanced electroanalytical methods for determination of different compounds, especially in biological and environmental matrixes. He is also scientifically involved in the national research project MNS-DIAG Micro- and Nano Systems in Chemistry and Biomedical Diagnostics.

Marcin Wieczorek was born in 1978 in Kielce, Poland. He received M.Sc. and Ph.D. degree in analytical chemistry at the Faculty of Chemistry Jagiellonian University in Kraków in 2002 and 2007, respectively. In 2008, he was honoured with the award of the Committee of Analytical Chemistry of Polish Academy of Sciences for his PhD thesis. Since 2007, he has been working in the Department of Analytical Chemistry at the Faculty of Chemistry Jagiellonian University. His main scientific interests focus on development of new analytical calibration strategies and on new methods in chemical analysis with the use of flow techniques.

Paweł Kościelniak is Professor at the Jagiellonian University and the Institute of Forensic Research (both Kraków, Poland). He is Head of Department of Analytical Chemistry (JU) and Laboratory for Forensic Research (JU). The main areas of his scientific interest are forensic chemistry, environmental analysis and flow analysis. He is involved in the development of novel analytical methods and procedures with special attention paid to such fundamental analytical issues as calibration, examination of interference effects, preconcentration and separation. He is an author of ca. 180 articles in these issues.

Agnieszka Moos received her M.Sc. degree in chemistry from Jagiellonian University in 2010 in Cracow. She is currently a Ph.D. student in the same University under supervision of Prof. Paweł Kościelniak. Her research activities have been focused on new techniques of biological sample preparation for forensic chemistry, mainly on solid phase extraction techniques.

Renata Wietecha-Posłuszny graduated and completed her M.Sc. (in 2000) and Ph.D. (in 2004) in advanced analytical and forensic chemistry at the Jagiellonian University in Krakow in collaboration with the Institute of Forensic Research in Krakow in Poland. The M.Sc. thesis was awarded by the Dr. Robel's Award as the best work in forensic area. She is currently working as Assistant Professor in Laboratory for forensic Chemistry at Jagiellonian University. Her main research subjects is developing modern and advanced methods of preparation and analysis of biological materials such as: human fluids and tissues for toxicological and forensic purpose. She takes part in national (MNS-DIAG) and international scientific projects (CITTES, TEMPUS) etc. She is a member of Polish Society of Toxicology and participant of The Eurolecturer Label.

Michał Woźniakiewicz was graduated M.Sc. (in 2003) and Ph.D. (with honours, in 2008) in advanced analytical and forensic chemistry at the Jagiellonian University in Krakow. He works as Assistant Professor in Laboratory for forensic Chemistry at Jagiellonian University. His research area covers developing advanced separation technique such as capillary electrophoresis, ultra high performance liquid chromatography, gas chromatography coupled mass spectrometry for toxicological and forensic purposes. He participates in national and international scientific and educational projects (MNS-DIAG, TEMPUS). He is a member of Polish Chemical Society and a participant of The Eurolecturer Label project.

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