Ankara University, Faculty of Pharmacy, Department of Analytical Chemistry, Tandogan, Ankara, Turkey
Anodic voltammetry of zolmitriptan at boron-doped diamond electrode
and its analytical applications
B. Uslu, D. Canbaz
Received July 23, 2009, accepted August 3, 2009
Pharmazie 65: 245–250 (2010)doi: 10.1691/ph.2010.9245
The electrooxidative behavior and determination of zolmitriptan at a boron-doped diamond electrode
were investigated using cyclic, linear sweep, differential pulse and square wave voltammetric tech-
niques. Zolmitriptan undergoes irreversible oxidation at a peak potential of about +0.9V (vs Ag/AgCl/3M
KCl). DPV and SWV techniques are proposed for the determination of zolmitriptan in phosphate
buffer at pH 3.03, which allows quantitation over the two different ranges (8×10−7–8×10−6M and
1×10−5–1×10−4M) in supporting electrolyte for both methods. A linear response was obtained in
phosphate buffer over two different ranges (6×10−7–8×10−6M and 1×10−5–1×10−4M) for spiked
serum samples at pH 3.03 for both techniques. The repeatability and reproducibility of the meth-
ods for all media were determined. The standard addition method was used in serum. Precision
and accuracy were also checked in all media. No electroactive interferences from the excipients and
endegenous substances were found in the pharmaceutical dosage form and the biological sample,
Boron-doped diamond (BDD) electrodes are becoming increas-
ingly attractive particularly in the field of electroanalysis due to
their unusual and extremely useful properties such as low and
stable background current (Spataru et al. 2002; Uslu and Ozkan
ous and non-aqueous solvent systems (Fujishima et al. 2002)
and good electroactivity towards certain organic species which
deactivate the surface of other conventional electrodes (Iniesta
BDD electrodes (Granger et al. 1999; Wirley et al. 2008; Zhao
et al. 2009; Uslu et al. 2008; Altun et al. 2009; Dogan-Topal
et al. 2007).
5-yl}methyl)-1,3-ozazolidin-2-one] is a selective serotonin
receptor agonist of the 1B and 1D subtypes. It is a triptan,
used in the acute treatment of migraine attacks with or without
aura and of cluster headaches (http:// www.medicinenet.com;
Peterlin et al. 2007). Migraine affects 18% of women and
6% of men. The significant impact of migraine results in a
huge burden for the individual, health services, and society.
Successful treatment of acute migraine attacks can reduce the
use of healthcare resources and improve health-related quality
of life (Oldman et al. 2002). The introduction of the trip-
tans in the 1990s revolutionized the treatment of migraine,
and a second-generation triptan, zolmitriptan, is highly effec-
tive in the oral treatment of acute migraine with or without
Spectrophotometry (Sankar et al. 2008; Raza et al. 2007;
Aydogmus and Inanlı 2007) and high-performance liquid
chromatography have been widely used for the quantitative
determination of triptans together with UV (Rao et al. 2005;
Yu et al. 2005), and mass spectrometry (Kılıc et al. 2007; Ding
et al. 2006; Chen et al. 2006; Zhang et al. 2004; Vishwanathan
et al. 2000) techniques. The sensitivity achieved by all these
procedures is highly satisfactory for the quantification of phar-
maceutical compounds. However, in some cases, a prior step is
required before quantification, involving extraction from mix-
tures with other compounds or from complex samples, which is
not economically feasible in routine analyses.
In this context, electroanalytical techniques have proved to be
compounds, since they are simple, cost little, and require rela-
tively short analysis times, without the need for derivatization
or time-consuming extraction steps. In addition to providing
high precision in pharmaceutical analyses, electroanalytical
Pharmazie 65 (2010)245
Fig. 1: Repetitive cyclic voltammograms of 8×10−5M zolmitriptan in 0.1M sulphuric acid (a); acetate buffer at pH 4.7 (b); Britton-Robinson buffer at pH 6.98 (c);
Britton-Robinson buffer at pH 9.01 (d)
fer mechanisms involved in a given reaction. This information
and pharmaceutical properties in the human organism, since the
reaction in humans is very similar to the redox process that
occurs when electroanalytical techniques are employed (Wang
1998). Among the electroanalytical techniques currently avail-
proved to be extremely sensitive methods for the detection of
No report has been published on the voltammetric determi-
nation of zolmitriptan in pharmaceutical formulations and no
monograph on zolmitriptan has yet been included in the official
This study therefore investigated the electrochemical behav-
ior of zolmitriptan and developed an analytical procedure to
quantify this compound in commercial formulations and serum
samples, employing BDD electrodes.
2. Investigations, results and discussion
2.1. Electrochemical behavior of zolmitriptan at BDD
Zolmitriptan appears to be an electroactive drug, but there
are no reports about the electrooxidation of zolmitriptan in
the scientific literature. Therefore, the electrochemical behav-
ior of zolmitriptan on a BDD electrode was studied by cyclic
voltammetry (CV), DPV and SWV. Various supporting elec-
using a BDD electrode (Fig. 1). The best results were obtained
with phosphate buffer at pH 3.03; peak and two wave poten-
tials, 0.89V, 1.23V and 1.33V vs Ag/AgCl (3.0molL−1KCl),
voltammograms the second and successive scans show a susb-
surface by oxidation product (Fig. 2). Voltammograms obtained
for zolmitriptan at a BDD electrode presented irreversible
A linear plot of peak current vs square root of the scan rate
was obtained, with a 0.9954 correlation coefficient, indicating
that the electrode process is controlled by mass transport. The
Fig. 2: Repetitive cyclic voltammograms of 8×10−5M zolmitriptan in phosphate
buffer at pH 3.03. Scan rate 100mVs−1. Numbers indicate number of scan
246 Pharmazie 65 (2010)
equation is given below in phosphate buffer at pH 3.03:
Ip (?A) = 0.2647 v½(mVs−1)
+0.272 (r : 0.9954, n : 9)(1)
A plot of logarithm of peak current versus logarithm of scan
rate gave a straight line with a slope of 0.48, very close to the
theoretical value of 0.5 for an ideal reaction for the diffusion-
controlled electrode (Kissenger and Heineman 1996).
The equation obtained is:
log ip (?A) = 0.4784 log v (mVs−1)
−0.493 (r : 0.9985, n : 9) (2)
A tafel plot was obtained in phosphate buffer at pH 3.03 with a
scan rate of 5mVs−1, beginning from a steady-state potential,
number of electrons participating in the electrode reaction pro-
cess can be calculated to be 1, assuming ? is 0.34. Assuming ?n
(the number of the electrons transferred in the rate determining
step)=n, the value of ? (the charge transfer coefficient) is 0.34.
system. These values together with the absence of a cathodic
wave in cyclic voltammetry (Fig. 2) indicated the irreversibil-
ity of the oxidation reaction of zolmitriptan. The peak potential
shifted to more positive potentials (about 51mV) in the anodic
direction when the scan rate increased from 5–1000mVs−1.
Fig. 3a presents the peak potential vs pH plot for zolmitriptan.
this pH potential is independent, with a break at pH 9.0, which
can be associated with the pKa of zolmitriptan of about 9.64
The relationship between Ep and pH at BDD electrode derived
using linear regression analysis can be expressed by the
Ep(mV) = 1057.83 − 54,108 pH (r : 0.9880,
between pH 2.00 − 9.00) (3)
The slope of ∼54.108mV per pH unit, being close to the
expected 59mV per pH unit, indicates that 1 proton and 1
electron are involved in the oxidation of zolmitriptan (Beltagi
et al. 2002).
A comparative study on 5-hydroxy indole, indole-3-acetic acid
of pH, in order to identify the oxidation process of zolmitrip-
tan, taking into account that the CV of these substances closely
matches the voltammogram of zolmitriptan. This molecule is
extensively metabolized in vivo, mainly through oxidative pro-
atom in the indole ring of the molecule, which is elecroactive in
both acidic and basic media, leading finally to hydroxylation of
the benzene ring (Suzen et al. 2003; Bozkaya et al. 2006; Goyal
et al. 1998; Yılmaz et al. 2001).
obtained in pH 3.03 phosphate buffer was plotted against
the logarithm of zolmitriptan concentration in the two ranges
(8×10−7– 8×10−6M (Part I) and 1×10−5–1×10−4M
(Part II)), linear relationships were obtained.
log i(?A) = 0.06 log C (M)
+ 0.49 Part I (r : 0.9913, n : 6)
Pharmazie 65 (2010)
Fig. 3: Effect of pH on zolmitriptan anodic peak potential (a) and peak current (b);
Zolmitriptan concentration 8×10−5M. (o) Britton-Robinson buffer (?)
Phosphate buffer (?) Sulphuric acid (♦) Acetate buffer
log i(?A) = 0.31 log C (M)
+1.88 Part II (r : 0.9940, n : 6) (5)
The slopes of these equations give the order of the reaction.
These kinetic parameters and the reaction order showed that
there was a mechanism related to the surface events, and the
reaction seems to be of first order.
2.2. Analytical applications
2.2.1. Validation of the analytical procedure
Two techniques, based on DPV and SW methods, were devel-
oped for the quantitative determination of zolmitriptan. The
peak potential versus pH plots were similar to those obtained by
CV, DPV and SW voltammetric techniques. The experimental
results showed that the shapes of the curve and maximum peak
current were better in phospahete buffer at 3.03 for analytical
applications (Fig. 3b).
Two linear calibration graphs were obtained over different con-
centration ranges between 1×10−6–8×10−6M (Part I) and
1×10−5–1×10−4M (Part II) for DPV and SWV. Character-
istics of these graphs (Part I) are reported in Table 1.
Validation of the optimized procedure for the quantitative
assay of zolmitriptan was examined by evaluating the limit of
Table 1: Regressiondataofcalibrationlines(forPartI)forquantitativedeterminationofzolmitriptanbyDPVandSWVinstandard
solution and human serum
Standard solutionSerum Standard solutionSerum
Measured potential (V)
Linearity range (M)
Slope (?A M−1)
SE of slope
SE of intercept
Repeatability of peak current (RSD%)
Repeatability of peak potential (RSD%)
Reproducibility of peak current (RSD%)
Reproducibility of peak potential (RSD%)
detection (LOD), limit of quantification (LOQ), repeatability,
reproducibility, accuracy, precision and recovery.
lowing equation (Riley and Roosanske 1996; Swartz and Krull
LOD: 3.3s/m; LOQ: 10s/m
and m is the slope of the calibration curve. The LOD and LOQ
values are also shown in Table 1.
Five experiments on 1×10−5M zolmitriptan were repeated
of peak current and peak potentials. The results are also shown
in Table 1. Repetition of sample analysis after 48h did not show
any significant change in the results of the analyses.
2.2.2. Assay of zolmitriptan in tablets
The results with standard solutions and the validation param-
eters obtained encourage the use of the proposed method as
described for the assay of zolmitriptan in tablet dosage forms.
of Zomig Rapimelt®tablets, DPV and SWV methods can used
for the direct determination of zolmitriptan using the relevant
calibration straight lines. The results show that the proposed
Table 2: Application of proposed voltammetric methods to
analysis of commercial tablets
Labeled claim (mg)
Amount found (mg)a
RSD % of recovery
aEach value is the mean of five experiments
of pure drug to various pre-analyzed formulations of zolmitrip-
tan and applying the procedure specified in the experimental
Recovery studies were carried out after the addition of known
amounts of the pure drug to various pre-analyzed formulations
of zolmitriptan. According to the results, excipients present in
the tablet do not interfere with the analysis (Table 2). There is
no official method for zolmitriptan in any pharmacopoeias. The
results demonstrate the validity of the proposed method for the
determination of zolmitriptan in tablets. These results show that
the proposed DPV and SWV methods have adequate precision
and accuracy and consequently can be applied to the determi-
from the excipients.
2.2.3. Determination of zolmitriptan in spiked serum
Fig. 4 illustrates DP and SW voltammograms obtained from
serum spiked at different concentrations of zolmitriptan using
the optimized conditions.
The peak current was linearly related to zolmitriptan concentra-
and 1×10−5–8×10−5M (Part II) according to the equations:
Ip(?A) = 2.04 × 104C (M) + 0.077
Part I (r : 0.9970, n : 7)(6)
Ip(?A) = 7.05 × 103C (M) + 0.41
Part II (r : 0.9900, n : 5)(7)
For SWVIp(?A) = 3.06 × 104C (M) + 0.055
Part I (r : 0.9952, n : 7)(8)
Ip(?A) = 0.17C (M) + 0.45 Part II (r : 0.9976, n : 5)
The estimated detection limits for both methods are also shown
in Table 1 for Part I. The amount of zolmitriptan in serum was
248 Pharmazie 65 (2010)
Table 3: Determination of zolmitriptan in human serum samples for DPV and SWV methods
Techniques Zolmitriptan added (M)Zolmitriptan founda(M)Average recovery (%)Bias (%)
aAverage value±SD of five experiments
calculated from the relevant linear regression (Part I) equation
recoveries of zolmitriptan were achieved from serum (Table 3).
As can be seen in Fig. 4, in the potential range where the ana-
lytical peak appeared there were no reduction compounds and
no extra noise peaks were found from biological materials.
Stability of serum samples kept in a refrigerator (+4◦C) was
tested by making five consecutive analyses of the sample over
a period of approximately 8h. No significant changes were
observed in the peaks were currents and potentials between the
first and last measurements.
Fig. 4: Differential pulse (a) and square wave (b) voltammograms obtained for
determination in spiked serum 1) blank; 2) 2×10−6M; 3) 4×10−6M; 4)
2×10−5M;5) 4×10−5M; 6) 6×10−5M zolmitriptan extract in phosphate
buffer at pH 3.03
Voltammetric experiments were performed using a BAS 100W (Bio-
analytical System, USA) electrochemical analyzer together with a
system consisting of a BDD (Windsor Scientific Ltd.; ф:3mm, diame-
ter) working electrode, a platinum wire counterelectrode and an Ag/AgCl
saturated KCl reference electrode. Before each experiment the BDD elec-
trode was polished manually with an aqueous slurry of alumina powder
(ф:0.01?m) on a damp smooth polishing cloth (BAS velvet polishing pad).
All measurements were made at room temperature.
The pH measurements were made using a model 538, WTW pH-meter
(Austria) with a combined electrode (glass-reference electrode) with an
accuracy of±0.05 pH.
The experimental conditions for DPV were: pulse amplitude, 50mV; pulse
width, 50ms; scan rate, 20mVs−1.
The experimenatl conditions for SWV were: pulse amplitude, 50mV; fre-
quency, 15Hz; potential step, 4mV.
3.2. Chemicals and standards
Zolmitriptan was kindly supplied by AstraZeneca (˙Istanbul, Turkey). The
other chemicals were reagent grade (Merck or Sigma).
A 1×10−3M stock solution of zolmitriptan was prepared in bidistilled
stock solution with the selected supporting electrolytes. Sulphuric acid (0.1
and 0.5M), phosphate buffer (0.2M, pH 2.00–8.05), acetate buffer (0.2M,
used as supporting electrolytes.
All solutions were kept in the dark and were used within 24h to avoid
decomposition. However voltammograms of the sample solutions recorded
one week after preparation did not show any appreciable change in assay
3.3. Pharmaceutical dosage form assay procedure
Six Zomig Rapimelt®tablets (each tablet containing 2.5mg zolmitriptan)
was thoroughly ground to a fine powder in a mortar and the amount of
sample corresponding to a stock solution of ca 1×10−3M was accurately
water. The mixture was sonicated for 30min until complete dissolution.
Appropriate solutions were prepared by taking suitable volumes of the
clear supernatant liquor and diluting with pH 3.03 phosphate buffer. Recov-
ery studies were performed to study the accuracy of the proposed method
and to check for possible interferences from common excipients. For these
experiments, known amounts of the pure drug were added to the previously
analyzed rapid melt tablet formulation of zolmitriptan. Each measurement
was repeated five times. These data gave an average zolmitriptan content
of 2.484±8,6×10−3mg for DPV and 2.488±1,2×10−2mg for SWV, in
inal content of the drug was calculated from the corresponding regression
3.4. Analysis of serum
Drug-free human blood, obtained from healthy volunteers (after obtain-
ing their written consent) was centrifuged (5000rpm) for 30min at room
temperature, and separated serum samples were stored frozen until assay.
An aliquot of serum sample was fortified with zolmitriptan dissolved in
bidistilled water to achieve a final concentration of 1×10−3M. Acetonitrile
removes serum proteins effectively and the appropriate ratio of volumes to
eliminate the protein was 1 to 1.5. After vortexing for 30s, the mixture was
then centrifuged for 10min at 5000rpm in order to eliminate serum protein
residues, and the supernatant was taken carefully.
Appropriate volumes of this supernatant were transferred into a volumetric
flask and diluted up to the volume with pH 3.03 phosphate buffer.
Quantifications were performed by means of the calibration curve method
from the related calibration equation. Inconclusion, the electrochemical
Pharmazie 65 (2010)249
behavior of zolmitriptan on a BDD electrode was established and studied
for the first time. Zolmitriptan undergoes irreversible oxidation at positive
potentials. The BDD electrode was shown to be perfectly suitable for anal-
ysis of zolmitriptan using the DPV and SWV techniques. The advantage of
the BDD electrode is that it is highly stable and sensitive.
the oxidation of their indole moiety over the BDD electrode. This behavior
provides a useful tool for detection and quantification of drugs at low levels
in biological samples.
This paper is not intended to be a study of the pharmacodynamic properies
for sample collection and results may be of no significance. It showed the
possibility of monitoring this drug compound, making the method likely to
be useful for pharmacokinetic and pharmacodynamic purposes.
Acknowledgements: This work was supported by Ankara Univer-
sity Scientific Research Project Foundation (Grant Nos: 20030803037
and 20030803043), Turkey. The authors also gratefully acknowledge
AstraZeneca Ind. for supplying zolmitriptan standard samples.
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