Voltammetric and RP-LC assay for the antidepressant drug mirtazapine: A validated method for the pharmaceutical dosage form


  • Fatma Ağın Karadeniz Technique University, Faculty of Pharmacy, Dept. of Analytical Chemistry, Trabzon, Turkey
  • Nurgül Karadaş Ankara University, Faculty of Pharmacy, Dept. of Analytical Chemistry, 06100, Ankara, Turkey Hitit University, Faculty of Science and Arts, Dept. of Chemistry, Corum, Turkey
  • Bengi Uslu Ankara University Faculty of Pharmacy
  • Sibel A. Özkan Ankara University




mirtazapine, voltammetry, liquid chromatography, stability-indicating studies, drug analysis


In the present paper, rapid, sensitive, selective, accurate and precise analytical methodologies were developed for the determination of the antidepressant drug mirtazapine (MIR) using voltammetry and liquid chromatography. In cyclic voltammetry (CV), MIR showed one sharp oxidation peak and one additional wave in acidic media in the anodic direction; at pH 5.50, the mirtazapine peak was single and sharp. Under optimized conditions, the peak current showed a linear dependence with concentration in the range between 0.212 and 26.54 µg/mL for glassy carbon (GC) and 1.06 and 26.54 µg/mL for boron-doped diamond (BDD) electrodes using differential pulse (DP) and square wave (SW) voltammetric techniques. The possible oxidation mechanisms are also discussed. A simple and fully validated reverse phase-liquid chromatography (RP-LC) method to test for MIR in tablets was developed using an X-Select RP-18 column (250x4.60 mm ID x 5µm) at 25ºC with methanol:water (30:70, v/v, containing 15 mM o-phosphoric acid) as the mobile phase adjusted to pH 3.0. The RP-LC method allowed quantification over a MIR concentration range of 1.0-18.0 µg/mL. MIR was exposed to thermal, photolytic, or oxidative stress, as well as acid and base hydrolysis conditions, and the stressed samples were assayed by the proposed LC method. The proposed methods allow for a number of cost- and time-saving benefits.

Author Biography

Bengi Uslu, Ankara University Faculty of Pharmacy

Ankara University Facult of Pharmacy

Dept of Analytical Chemistry


The Merck Index, 13th ed., Whitehouse Station, NJ,

P. M. Hartmann, Mirtazapine: a newer antidepressant,

Am. Fam. Phys., 59, 159–161 (1999).

D. Nutt, Mirtazapine: pharmacology in relation to adverse

effects, Acta Psych. Scand., 96, 31–37 (1997).

S. C. Sweetman, Martindale, The Extra Pharmacopoeia,

th ed., Pharmaceutical Press, L o n d o n ,

X. Hong, Y. Yao, S. Hong, C. Lei, LC–MS–MS

analysis of mirtazapine in plasma and determination

of pharmacokinetic data for rats, Chromatogr., 68,

–70 (2008).

R. Mandrioli, L. Mercolini, N. Ghedini, C. Bartoletti,

S. Fanali, M. A. Raggi, Determination of the antidepressant

mirtazapine and its two main metabolites in

human plasma by liquid chromatography with fluorescence

detection, Anal. Chim. Acta., 556, 281–288


C. Pistos, M. Koutsopoulou, I. A. Panderi, A validated

liquid chromatographic tandem mass spectrometric

method for the determination of mirtazapine and

demethylmirtazapine in human plasma: Application

to a pharmacokinetic study, Anal. Chim. Acta., 514,

–26 (2004).

P. Ptacek, J. Klima, J. Macek, Determination of mirtazapine

in human plasma by liquid chromatography,

J. Chromatogr. B: Anal. Tech. Biomed. Life Sci., 794,

–328 (2003).

T. Romiguieres, F. Pehourcq, M. Matoga, B. Begaud,

C. Jarry, Determination of mirtazapine and its

demethyl metabolite in plasma by high-performance

liquid chromatography with ultraviolet detection:

Application to management of acute intoxication,

Journal of Chromatogr. B: Anal. Tech. Biomed. Life

Sci., 775, 163–168 (2002).

L. Labat, P. Dallet, E. Kumer, J. P. Dubost, Spectrophotometric,

spectrofluorimetric, HPLC and CZE determination

of mirtazapine in pharmaceutical tablets,

J. Pharm. and Biomed. Anal., 28, 365–371 (2002).

B. Saini, M. Kaushal, G. Bansal, A validated direct

spectrofluorimetric method for quantification of mirtazapine

in human whole blood, Spectroscopy., 24,

–649 (2010).

R. M. Youssef, Determination of mirtazapine in

spiked human plasma and tablets by first derivative

spectrofluorimetric method, Saudi Pharm. J., 18,

–49 (2010).

D. R. Kumar, V. N. Lakshmi, S. V. M Vardhan, C.

Rambabu, Bioscien. Biotech. Res. Asia., 5, 863–866


N. Karaşen, S. Altinöz, Determination of mirtazapine

in tablets by UV spectrophotometric and derivative

spectrophotometric methods, J. Pharm. and Biomed.

Anal., 24, 11–17 (2000).

B. Uslu, S. A. Ozkan, Electroanalytical application of

carbon based electrodes to the pharmaceuticals, Anal.

Lett., 40, 817–853 (2007).

B. Uslu, S. A. Ozkan, Solid electrodes in electroanalytical

chemistry: Present applications and prospects

for high-throughput screening of drug compounds,

Comb. Chem. High Through. Screen., 10, 495–513


B. Uslu, S. A. Ozkan, H. Y. Aboul-Enein, Analysis of

pharmaceuticals and biological fluids using modern

electroanalytical techniques, Crit. Rev. Anal. Chem.,

, 155–181 (2003).

M. R. Symth, J. G. Vos, Analytical Voltammetry, Vol.

XXVIII of series, Comprehensive Analytical Chemistry,

Amsterdam, 1992.

R. N. Goyal, S. Chatterjee, A. R. S. Rona, A singlewall

carbon nanotubes modified edge plane pyrolytic

graphite sensor for determination of methylprednisolone

in biological fluids, Talanta, 80, 586–592


J. Wang, Electroanalytical Techniques in Clinical

Chemistry and Laboratory Medicine VCH, New

York, 1988.

C. Wang, J. Guan, Q. Qu, G. Yang, X. Hu, Voltammetric

determination of sinomenine in biological

fluid using a glassy carbon electrode modified by a

composite film of polycysteic acid and carbon nanotubes,

Com. Chem. High Through. Screen., 10, 595–


B. Uslu, S. A. Ozkan, H. Y. Aboul-Enein, Electrochemical

study of S-adenosyl-L-methionine and its

differential pulse and square wave voltammetric determination,

Electroanalysis, 14, 736–740 (2002).

M. Gumustas, S. A. Ozkan, Electrochemical evaluation

and determination of antiretroviral drug fosamprenavir

using boron-doped diamond and glassy carbon

electrodes, Anal. Bioanal. Chem., 397, 189–203


D. Kul, M. Gumustas, B. Uslu, S. A. Ozkan, Electroanalytical

characteristics of antipsychotic drug

ziprasidone and its determination in pharmaceuticals

and serumsamples on solid electrodes, Talanta, 82,

–295 (2010).


Remeron-PM. Product monograph template-standard.

S. A. Ozkan, Electroanalytical Methods in Pharmaceutical

Analysis and Their Vaildation, 1st ed., HNB

Pub., 2011.

C. M. Riley, T. W. Rosanske, Development and Validation

of Analytical Methods, Elsevier, Amsterdam,

the Netherlands, 1996.

ICH, Stability testing of new drug substances and

products (Q1AR): International Conference on Harmonization

IFPMA, Geneva, 2000.

ICH Harmonised Tripartite Guideline (2005) Validation

of Analytical Procedures: Text and Methodology


N. L. Monser, M. Toumi, K. Boujlel, Determination

of naproxen in pharmaceuticals by differential pulse

voltammetry at a platinum electrode, Anal. Chim.

Acta., 495, 69–75 (2003).

B. Uslu, S. A. Ozkan, A rapid HPLC assay for the

determination of lamivudine from pharmaceuticals

and human serum, Anal. Chim. Acta., 462, 49 (2002).

S. A. Ozkan, B. Uslu, P. Zuman, Electrochemical

oxidation of sildenafil citrate (Viagra) on carbon electrodes.

Anal. Chim. Acta., 501, 227 (2004).

H. Lund, O. Hammerich, Organic Electrochemistry,

Revised and Expanded, 4th ed., Marcel Dekker Inc.

Pub., 2001.

J. Grimshaw, Electrochemical Reactions and Mechanism

in Organic Chemistry, 1st ed., Elsevier Science

Publication, 2000.

S. Suzen, B. T. Demircigil, E. Buyukbıngol, S. A.

Ozkan, Electroanalytical evaluation and determination

of 5-(3ʹ-indolal)-2-thiohydantoin derivatives by

voltammetric studies: Possible relevance to in vitro

metabolism, New J. Chem., 27, 1007 (2003).




How to Cite

Ağın, F., Karadaş, N., Uslu, B., & Özkan, S. A. (2013). Voltammetric and RP-LC assay for the antidepressant drug mirtazapine: A validated method for the pharmaceutical dosage form. Macedonian Journal of Chemistry and Chemical Engineering, 32(1), 41–55. https://doi.org/10.20450/mjcce.2013.91



Analytical Chemistry