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Determination of Domperidone in Tablet Dosage Form by Anodic Differential Pulse Voltammetry
Determination of Domperidone in Tablet Dosage Form by Anodic Differential Pulse Voltammetry
http://france.elsevier.com/direct/FARMAC/
Original article
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 2. Experimental
2.1. Reagents
Domperidone (DOM), or 5-chloro-1- [1-[3-(2,3-dihydro-
2-oxo-1H-benzimidazol-1-yl)propyl]-4-piperidinyl]-1,3- Domperidone and Motilium® tablets were obtained from
dihydro-2H-benzimidazol-2-one is a dopamine antagonist Janssen–Cilag Pharmaceutics (Beerse, Belgium). All the other
used as an antiemetic for the short-term treatment of nausea chemicals used in the experiments were of analytical grade.
and vomiting of various etiologies [1]. Double distilled water was used for preparation of the solu-
Methods for the assay of domperidone in tablet dosage tions. Stock solution of Domperidone was prepared in metha-
forms are usually based on spectrophotometric [2] or calori- nol. Dilutions were made from this solution to the final con-
metric determinations [3]. Liquid chromatographic methods centrations with water. A stock Britton–Robinson (BR) buffer
have been developed to monitor the levels of domperidone in solution of 0.04 M glacial acetic acid, ortho-phosphoric acid
plasma and tissue fluids [4]. and boric acid was prepared. Buffer solutions of different pH
The aim of this study was to examine the voltammetric values were then prepared by addition of 0.2 M sodium
behavior of the domperidone molecule based upon the oxi- hydroxide Fig. 1.
dation on the surface of a glassy carbon electrode and also to
2.2. Apparatus
determine domperidone in the tablets by differential pulse
voltammetry (DPV) in a tablet dosage form. The validity of All voltammetric experiments were performed using a
the method was tested comparing the results to those of Model AEW2 analytical electrochemical analyzer controlled
UV-spectrophotometry, which has been accepted as a com-
parison method. All the results were evaluated statistically
by common statistical tests.
* 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
2.3. Procedure
3.1. Effect of pH
dation reaction. (ii) The peak current increased steadily (iii) Table 1
the peak current function, ip/ACv1/2 exhibited almost con- Application of the proposed voltammetric method to the determination of
domperidone in Motilium® tablets
stancy. If the polishing was not carried out between two sweep
Item DPV Official titrimetric
runs, a decrease in the peak current was observed. This indi-
method [6]
cates the possibility of adsorption. A straight line was obtained Mean (%) 101.40 98.35
when ip was plotted against v1/2. This reveals that the anodic S.D. 1.10 1.15
oxidation is diffusion controlled. A straight line was observed N 6 6
when Ep was plotted against log v; described by the equation: t-value 1.69 (2.78)
Ep = 0.088 log v + 0.0017. From the slope of the straight line, F-value 1.778 (6.388)
the ana value (where a is the charge transfer coefficient and Figures in parentheses are the corresponding theoretical t- and F-values
na is the number of electrons involved in the rate-determining (P = 0.05).
step) was calculated by using the formula, DE/Dlog v = –
lated from five independent runs of 1.0 × 10–5 M domperi-
30/ana. The a value was found to be 0.34, confirming the
done solution. The relative standard deviations were calcu-
irreversible nature of the oxidation reaction.
lated to be 0.35 and 1.25% for peak potential and peak current,
The number of protons (p) transferred in the rate-
respectively.
determining step was calculated from the expression:
DEp/DpH = /0.059 p/a na. The ana and p values are consis-
3.4. Interference studies
tent with one electron–one proton transfer involved in the rate-
determining step. It seems reasonable to conclude that the
In order to known whether the matrix affects the analysis,
nitrogen atom of the amide on 1 e–, 1 H+ oxidation gives a
recovery studies for the accuracy of the method were per-
free radical species in the rate-determining step.
formed. The excipients were added, according to the manu-
facturer’s batch formula, to known amounts of domperidone
3.3. Effect of concentration
in BR buffer pH 8.0. The magnitude of the peak current for
domperidone showed no deviation of more than 3% from the
Using DPV employing the optimum conditions (Pulse
peak current of the solution containing no interfering addi-
amplitude, 50 mV; pulse width 30 ms; scan rate, 10 mV s−1),
tives, indicating that there were no serious interferences to
a linear calibration curve was obtained for domperidone in
the method.
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 4. Application of the method to Motilium® tablets
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 The validity of the method proposed in this study was
Sy/x is the standard deviation of y-residuals and b is the slope applied to a Motilium® tablets, containing 10 mg domperi-
of the calibration plot. A set of voltammograms illustrating done maleate. Tablets were processed as described under the
the variation of peak height with concentration is given in experimental studies and optimum voltammetric conditions
Fig. 4. The reproducibility of the measurement was calcu- 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