Il Farmaco 60 (2005) 830–833

http://france.elsevier.com/direct/FARMAC/

Original article

“Determination of domperidone in tablet dosage form by anodic

differential pulse voltammetry”
Tarek Wahdan *, Nadia Abd El-Ghany
Chemistry Department, Faculty of Education, Suez Canal University, 45111 Al-Arish, Egypt
Received 8 March 2005; accepted 2 July 2005

Available online 31 August 2005

Abstract

A differential pulse voltammetric method was described for the determination of domperidone. The method was based on the anodic
oxidation of domperidone on a glassy carbon electrode at +0.64 V vs. SCE in Britton–Robinson buffer solution of pH 2.3. The reversibility of
the oxidation was tested by cyclic voltammetry; the electrode process is irreversible and diffusion–adsorption controlled. Calibrations are
linear over the range 1.0 × 10–6–2.0 × 10–5 M of domperidone with a detection limit of 4.0 × 10–7 M. The method was applied, without any
interference from the excipients, to the determination of the drug in a tablet dosage form.
© 2005 Elsevier SAS. All rights reserved.

Keywords: Domperidone; Differential pulse voltammetry; Glassy carbon electrode; Electrochemical oxidation; Pharmaceutical analysis

1. Introduction
Domperidone (DOM), or 5-chloro-1- [1-[3-(2,3-dihydro-
2-oxo-1H-benzimidazol-1-yl)propyl]-4-piperidinyl]-1,3-
dihydro-2H-benzimidazol-2-one is a dopamine antagonist
used as an antiemetic for the short-term treatment of nausea
and vomiting of various etiologies [1].
Methods for the assay of domperidone in tablet dosage
forms are usually based on spectrophotometric [2] or calori-
metric determinations [3]. Liquid chromatographic methods
have been developed to monitor the levels of domperidone in
plasma and tissue fluids [4].
The aim of this study was to examine the voltammetric
behavior of the domperidone molecule based upon the oxi-
dation on the surface of a glassy carbon electrode and also to
determine domperidone in the tablets by differential pulse
voltammetry (DPV) in a tablet dosage form. The validity of
the method was tested comparing the results to those of
UV-spectrophotometry, which has been accepted as a com-
parison method. All the results were evaluated statistically
by common statistical tests.
2. Experimental
2.1. Reagents
Domperidone and Motilium® tablets were obtained from
Janssen–Cilag Pharmaceutics (Beerse, Belgium). All the other
chemicals used in the experiments were of analytical grade.
Double distilled water was used for preparation of the solu-
tions. Stock solution of Domperidone was prepared in metha-
nol. Dilutions were made from this solution to the final con-
centrations with water. A stock Britton–Robinson (BR) buffer
solution of 0.04 M glacial acetic acid, ortho-phosphoric acid
and boric acid was prepared. Buffer solutions of different pH
values were then prepared by addition of 0.2 M sodium
hydroxide Fig. 1.
2.2. Apparatus
All voltammetric experiments were performed using a
Model AEW2 analytical electrochemical analyzer controlled

* Corresponding author.
E-mail address: tarekwahdan@yahoo.com (T. Wahdan). Fig. 1. Chemical structure of domperidone.

0014-827X/$ - see front matter © 2005 Elsevier SAS. All rights reserved.
doi:10.1016/j.farmac.2005.07.001
 T. Wahdan, N.A. El-Ghany / Il Farmaco 60 (2005) 830–833 831

via PC computer using the ECprog3 electrochemistry soft-

ware (Sycopel, UK), connected to C-2 stand with a three-
electrode configuration: a glassy carbon (U = 3 mm) work-
ing electrode, an Ag-AgCl-3 M KCl reference electrode and
a platinum wire counter electrode. OriginPro 7.0 software was
used for the transformation of the initial signal. A CG 808
(Schott Geräte, Germany) digital pH meter with glass com-
bination electrode served to carry out the pH measurements.

2.3. Procedure

Ten milliliters of the supporting electrolyte solution was

placed in the voltammetric cell. After measurement of the
blank solution, the appropriate amount of domperidone solu-
tion is added and the anodic potential sweep was carried under
different operational parameters. All measurements were car-
ried out at room temperature. The peak heights were evalu-
Fig. 2. Effect of pH on (a) peak potential and (b) peak current in BR buffer
using DPV at glassy carbon electrode. Domperidone concentration, 1.0 × 10–
–1
5 M; scan rate, 10 mV s ; pulse amplitude, 50 mV; pulse width, 30 s.

ated by means of the tangent method. The electrode surface

was hand-polished with 0.5 µm particle size alumina; then it
was rinsed with distilled water and dried with a non-abrasive
tissue paper before each experiment.
2.4. Analysis of tablets dosage form
Twenty Motilium® tablets each containing 10 mg domp-
eridone maleate, were weighed accurately, reduced to a homo-
geneous fine powder in a mortar. An amount equal to the cal-
culated average tablet mass was transferred to a 10-ml flask,
and methanol was added to dissolve the active material [5,6].
The mixture was sonicated for 10 min to achieve complete
dissolution and made up to the final volume with methanol
An aliquot of clear supernatant liquor was then transferred to
the voltammetric cell containing 10 ml of BR buffer (pH 8.0)
to yield a final concentration of 1.0 × 10–5 M domperidone.
The differential pulse voltammogram was subsequently
recorded employing the optimized conditions. To quantify the
unknown amount of domperidone in solution, a multiple stan-
dard addition procedure was employed [7,8].
Therefore, it was decided to carry out the rest of the studies at
pH 8.0.
3.2. Cyclic voltammetry
A typical cyclic voltammogram of 5.0 × 10–4 M domperi-
done at glassy carbon electrode in BR buffer at pH 8.0 is
shown in Fig. 3. Domperidone has an anodic peak at 0.800 V.
In subsequent cycle (curve 2), the peak height significantly
decreases and the signal is hardly discernible from the base-
line, indicating that the passivation of the GCE electrode sur-
face by the polymeric oxidation product or fouling of the GCE
electrode by oxidation products. On the reverse scan, no
cathodic peak was observed at scan rates of 25–300 mV s–1
indicating that the domperidone oxidation is an irreversible
process.
As the sweep rate was increased from 20 to 500 mV s−1 at
a fixed concentration of 5.0 × 10–4 domperidone: (i) the peak
potential shifted anodically, as expected for irreversible oxi-

3. Results and discussion

3.1. Effect of pH

The DPV of domperidone was recorded at the glassy car-

bon electrode over a wide pH range (pH 2.0–11.0). At all the
pH values investigated, one well-defined oxidation peak was
observed. The effect of pH on the peak potential (Ep) and
peak current (ip) of the oxidation peak of domperidone [8–11]
is shown in Fig. 2. The graph of Ep versus pH clearly indi-
cates that the peak shifts to less positive potentials with
increasing pH, as shown in Fig. 2a. Between pH 2 and 5 the
slope of the graph was 45 mV pH. The effect of the solution
pH on the peak enhancement is also shown in Fig. 2b. The Fig. 3. Cyclic voltammograms of 5.0 × 10–4 M domperidone solution on
best results with respect to signal enhancement accompanied glassy carbon electrode in BR buffer at pH 8.0. Scan rate, 100 mV s−1. The
by sharper response was obtained with BR buffer at pH 8.0. dotted lines represent blank solution.
832 T. Wahdan, N.A. El-Ghany / Il Farmaco 60 (2005) 830–833
dation reaction. (ii) The peak current increased steadily (iii)
the peak current function, ip/ACv1/2 exhibited almost con-
stancy. If the polishing was not carried out between two sweep
runs, a decrease in the peak current was observed. This indi-
cates the possibility of adsorption. A straight line was obtained
when ip was plotted against v1/2. This reveals that the anodic
oxidation is diffusion controlled. A straight line was observed
when Ep was plotted against log v; described by the equation:
Ep = 0.088 log v + 0.0017. From the slope of the straight line,
the ana value (where a is the charge transfer coefficient and
na is the number of electrons involved in the rate-determining
step) was calculated by using the formula, DE/Dlog v = –
30/ana. The a value was found to be 0.34, confirming the
irreversible nature of the oxidation reaction.
The number of protons (p) transferred in the rate-
determining step was calculated from the expression:
DEp/DpH = /0.059 p/a na. The ana and p values are consis-
tent with one electron–one proton transfer involved in the rate-
determining step. It seems reasonable to conclude that the
nitrogen atom of the amide on 1 e–, 1 H+ oxidation gives a
free radical species in the rate-determining step.
3.3. Effect of concentration
Using DPV employing the optimum conditions (Pulse
amplitude, 50 mV; pulse width 30 ms; scan rate, 10 mV s−1),
a linear calibration curve was obtained for domperidone in
the range 3.0 × 10–6 M – 5.0 × 10–5 M. The characteristics of
this graph were slope 0.01179 µA µM−1, current intercept
0.18964 µA and correlation coefficient r = 0.999. The limit
of detection of the procedure was found to be 1.0 × 10–6 M,
which were estimated [9–14] as: LOD = 3Sy/x/b [15], where
Sy/x is the standard deviation of y-residuals and b is the slope
of the calibration plot. A set of voltammograms illustrating
the variation of peak height with concentration is given in
Fig. 4. The reproducibility of the measurement was calcu-
Fig. 4. Differential pulse voltammograms for increasing concentrations of
domperidone in BR buffer at pH 8.0 on glassy carbon electrode. Scan rate,
10 mV s–1; pulse amplitude, 50 mV; pulse width, 30 ms. Domperidone
concentration: (1) 7.5 × 10–6 M (2) 1.5 × 10–5 M (3) 2.25 × 10–5 M and (4)
3.0 × 10–5 M; the dotted lines represent blank solution.
Table 1
Application of the proposed voltammetric method to the determination of
domperidone in Motilium® tablets
Item DPV Official titrimetric
method [6]
Mean (%) 101.40 98.35
S.D. 1.10 1.15
N 6 6
t-value 1.69 (2.78)
F-value 1.778 (6.388)
Figures in parentheses are the corresponding theoretical t- and F-values
(P = 0.05).
lated from five independent runs of 1.0 × 10–5 M domperi-
done solution. The relative standard deviations were calcu-
lated to be 0.35 and 1.25% for peak potential and peak current,
respectively.
3.4. Interference studies
In order to known whether the matrix affects the analysis,
recovery studies for the accuracy of the method were per-
formed. The excipients were added, according to the manu-
facturer’s batch formula, to known amounts of domperidone
in BR buffer pH 8.0. The magnitude of the peak current for
domperidone showed no deviation of more than 3% from the
peak current of the solution containing no interfering addi-
tives, indicating that there were no serious interferences to
the method.
4. Application of the method to Motilium® tablets
The validity of the method proposed in this study was
applied to a Motilium® tablets, containing 10 mg domperi-
done maleate. Tablets were processed as described under the
experimental studies and optimum voltammetric conditions
were employed for the quantification. No interference was
observed from the excipients of the tablets. The official titri-
metric method served as a comparison method. The results
of the methods for six samples were compared to each other
at the 95% probability level. The results of the statistical evalu-
ations are given in Table 1. According to the results of t- and
F-tests, insignificant differences appeared between the two
methods.
5. Conclusion
Based on the above results, we can state that the method
developed is a good tool for domperidone determination in
tablets. The principal advantage of the proposed voltammet-
ric method over the already published procedures for the deter-
mination of domperidone is the rapidity of analysis that
involves no sample preparation other than dissolving and
transferring an aliquot to the background electrolyte, and does
not require such operations as filtration and extraction. It is to
note that excipients presented in tablets do not interfere with
the analysis.
 T. Wahdan, N.A. El-Ghany / Il Farmaco 60 (2005) 830–833
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