Spectrophotometeric Determination of Dexrabeprazole Sodium and Domperidone Maleate in Bulk and Capsule Dosage Form by First Order Derivative Spectroscopy
Priyanka S. Shedpure, Priyanka A. Patel, Sanjay D. Sawant and Manjusha N. Dole*
Department of Pharmaceutical Chemistry, Smt. Kashibai Navale College of Pharmacy, Kondhwa, Pune-411048, Maharashtra, India
*Corresponding Author E-mail: manjushadole@rediffmail.com
ABSTRACT:
In the present work, a simple, economical, precise and accurate method for determination of Dexrabeprazole sodium (DEX) and Domperidone maleate (DOM) in combined dosage form has been developed. Dexrabeprazole sodium is a proton pump inhibitor and Domperidone maleate is an antiemetic drug. In combination the drugs are commercially available as capsule dosage form for oral administration. Literature survey reveals one spectrophotometric method and one RP-HPLC method has been reported for DEX in combined dosage form. No analytical method is available for estimation of DEX in single dosage form. Domperidone alone or in combination with other drugs is reported to be estimated by spectrophotometry, HPLC, LC, LC-MS, and HPTLC method. A first order derivative spectroscopic method has been developed for determination of Dexrabeprazole sodium (DEX) and Domperidone maleate (DOM) in the capsule dosage form in which derivative amplitudes were measured at selected wavelengths. The wavelengths at 253 nm and 266 nm in the first order derivative spectra were selected to determine DOM and DEX, respectively. Beer’s law is obeyed in the concentration range of 2-36 μg/ml for DEX and 6-36 μg/ ml and for DOM. The results of analysis have been validated statistically, which confirm the accuracy and reproducibility of the method. Recovery was found in the range of 99.94 – 102.5 % for DEX and 99.88 – 100.08 % for DOM. The proposed method was applied successfully to determine uniformity of contents in commercial capsule formulations.
KEYWORDS: Dexrabeprazole sodium, Domperidone maleate, first order derivative, UV- spectrophotometery.
INTRODUCTION:
Dexrabeprazole sodium (DEX) is chemically 2-{[4-(3-methoxy propoxy)-3-methylpyridin-2-yl]methyl sulfinyl}-1H-benzimidazole. Dexrabeprazole is R configuration of Rabeprazole. It is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the gastric H+ K+ ATPase enzyme system at the secretory surface of the gastric parietal cell.(1) Domperidone maleate (DOM) is peripheral dopamine antagonist. It is official in British Pharmacopoeia and European Pharmacopoeia(2,3). Chemically it is 5-chloro-1-[1-[3-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)propyl]- piperidin-4-yl]-1,3-dihydro-2H benzimidazol-2-one2.Literature survey reveals one spectrophotometric method(4) and one RP-HPLC method(5) has been reported for DEX in combined dosage form.
No analytical method is available for DEX in single dosage form. Domperidone alone or in combination with other drugs is reported to be estimated by spectrophotometry6-7, HPLC8-11, LC12, LC-MS13, and HPTLC14.
MATERIAL AND METHODS:
Instrumentation: For the present study JASCO double beam UV/Visible spectrophotometer (Model V-630) was used with slit width fixed at 1.5nm ,equipped with spectra manager software (Version 1.5). A pair of 1-cm matched quartz cells was used to measure the absorbance of solution. The samples were weighed on electronic analytical balance (Contech Model CB-50)
Materials: Gift samples of Dexrabeprazole sodium and Domperidone were provided by Emcure Pharmaceuticals Limited, Pune, India. The pharmaceutical dosage form used in this study was Dexpure D.(Emcure Pharmaceuticals Limited). Each hard gelatin capsule contains10mg DEX (as an enteric coated) and 30mg of DOM (as a sustained release).
Solvent: Methanol Spectroscopic grade (Thomas Baker), 0.1N NaOH
Table1: Instruments
|
Name |
Model |
Manufacturer |
|
UV/Visible spectrophotometer Electronic analytical balance |
V-630 CB-50 |
Jasco Contech |
First Order Derivative Spectrophotometric Method:(15)
Preparation of standard stock solutions:
Standard stock solutions of both DEX and DOM were prepared by dissolving accurately weighed 10 mg of DEX and 10mg of DOM separately in 25ml of methanol in 100ml volumetric flasks. Final volume was made up to 100ml with methanol to get stock solution of each containing 100µg/ml of both DEX and DOM. From this, suitable dilutions were made in 0.1N NaOH to get the working standard solutions of DOM and DEX in the increasing concentration range.
Selection of wavelength for analysis:
By appropriate dilution of standard stock solution of DEX and DOM, 10 µg/ml of DEX and 30 µg/ml of DOM were prepared separately. The standard solutions were then scanned in the spectrum mode from 400 nm to 200 nm. The spectra were converted into first order derivative spectra and their overlay was taken (fig.no.1). From the overlain spectra of both drugs, DOM showed considerable absorbance at 253nm, which is zero crossing point of DEX. Further, DEX showed considerable absorbance at 266nm which is zero crossing point for DOM. Therefore, wavelengths 253nm and 266nm were employed for determination of DOM and DEX respectively without interference of other drug.
FIG 1: OVERLAY OF FIRST ORDER DERIVATIVE SPECTRA OF 10𝜇g/ml DEX AND DOM 30 µg/ml
Linearity:
10mg of DEX and DOM were weighed separately in 100ml of volumetric flask, and dissolved using methanol to get 100𝜇g/ml each. Further aliquots were prepared by using 0.1 N NaOH. The absorbances of the derivatised spectra were measured at 253 nm and 266nm for DOM and DEX, respectively. For DEX linearity was observed in the concentration range of 2-36 µg/ml and for DOM linearity was observed in the concentration range of 6-36 µg/ml.
Analysis of synthetic mixture of DEX and DOM:
From the stock solutions, 100 µg/ml of DEX and DOM each, sample solution containing 10 µg/ml of DEX and 30 µg/ml of DOM were prepared. The absorbance of the sample solution was measured at 253 nm and 266 nm. The concentration of DEX and DOM in the sample solution was calculated by substituting the dA/dλ253nm and dA/dλ266nm nm in the equations I and II.
CDEX= dA/dλ266nm – Intercept (C )/slope (m) ……….… [I]
CDOM = dA/dλ253nm – Intercept (C )/slope (m) ….….… [II]
Analysis of the marketed formulation:
For the estimation of drugs in the commercial formulations, twenty tablets containing 10 mg of DEX and 30 mg of DOM were weighed and average weight was calculated. The tablets were crushed and powdered in glass mortar. For the analysis of drugs, quantity of powder equivalent to 10 mg of DEX and 30 mg of DOM was transferred to 100 ml volumetric flasks and dissolved in sufficient quantity of methanol. It were kept for ultrasonication for 90 mins and was filtered through Whatmann filter paper no. 42 to get stock solution of 100µg/ml. Aliquots were prepared by using 0.1N NaOH and the solutions were scanned and the first order derivative spectra was recorded. The assay procedure was repeated six times (n=6). The results of the analysis of the marketed formulations are given in table no.2.
Precision:
The reproducibility of the proposed method was determined by performing tablet assay at different time intervals on same day (Intra-day precision) and on three different days (Inter-day precision).
The LOD and LOQ were separately determined based on calibration curve. The slope and the y intercept of the linearity plot was determined. For each of the six replicate determinations the residual standard deviation (σ) of the y intercepts of the regression line was computed. From these values LOD and LOQ were determined on the basis of response and slope of the regression equation. The results are given in table no.4.
Table no.2 Results of marketed formulation analysis
|
Amt. taken ( µg/ml ) |
dA/dλ
|
Amount of drug found ( µg/ml ) |
% Amt. found |
||||
|
DEX |
DOM |
266 nm |
253 nm |
DEX |
DOM |
DEX |
DOM |
|
10 |
30 |
0.0156 |
0.0046 |
10.1 |
30.12 |
101 |
100.4 |
|
% Mean amt. estimated* |
± S.D.* |
C.O.V.* |
%R.S.D. |
||||
|
DEX |
DOM |
DEX |
DOM |
DEX |
DOM |
DEX |
DOM |
|
102 |
100.01 |
0.00006 |
0.00018 |
0.01140 |
0.10677 |
0.67 |
0.76 |
*Average of six determinations.
LOD= 3.3σ/ slope
LOQ=10σ/slope
Table no. 4: LOD and LOQ of DEX and DOM
|
Parameter |
DEX |
DOM |
|
Limit of detection (µg) |
0.75 |
0.91 |
|
Limit of quantitation (µg) |
1.28 |
1.47 |
Table no. 5: Results of recovery studies
|
Level of recovery (%) |
Amt. taken ( µg/ml ) |
Amt of std. added ( µg/ml ) |
Total amt. recovered ( µg/ml ) |
% Recovery
|
||||
|
DEX |
DOM |
DEX |
DOM |
DEX |
DOM |
DEX |
DOM |
|
|
80 |
5 |
15 |
4 |
12 |
4.1 |
12.13 |
102.5 |
101.08 |
|
100 |
5 |
15 |
5 |
15 |
4.97 |
14.98 |
99.94 |
99.88 |
|
120 |
5 |
15 |
6 |
18 |
6.2 |
18.1 |
101.3 |
100.55 |
Table no. 6: Statistical evaluation of recovery studies.
|
Level of recovery (%) |
± S.D. * |
C.O.V. * |
%RSD |
|||
|
DEX |
DOM |
DEX |
DOM |
DEX |
DOM |
|
|
80 |
0.00015 |
0.00019 |
0.01224 |
0.01378 |
1.7 |
0.7 |
|
100 |
0.00013 |
0.00033 |
0.01140 |
0.01816 |
1.4 |
1.1 |
|
120 |
0.00018 |
0.0054 |
0.01341 |
0.07348 |
1.6 |
1.7 |
Table No – 3: Result of marketed formulation analysis
|
Method |
Label claim |
% Label Claim*(Mean±SD) |
%RSD |
|
First order Derivative method |
DEX 10mg |
102 ± 0.00015 |
1.56 |
|
DOM 30mg |
100.4 ± 0.0019 |
1.16 |
*Average of six determinations
Accuracy:
To check the accuracy of the proposed method, recovery studies were carried out at 80 %, 100 %, and 120 % level of the test concentration as per the ICH guidelines.(16) To the sample solution solution of 15μg/ml of domperidone and 5 μg/ml of dexrabeprazole sodium an increasing aliquots from working standard solution of domperidone and dexrabeprazole sodium were added respectively. The solutions were measured at 253 nm for domperidone and 266 nm for dexrabeprazole sodium and % recovery of the sample was calculated. The results of the recovery studies and its statistical evaluation are summarized in table no 5 and 6.
RESULTS AND DISCUSSION:
For the proposed method, linearity, accuracy studies and precision were performed. Linearity was observed in the concentration range of 2-36μg/ml and 6-36 μg/ml for DEX and DOM respectively. The results of commercial tablet formulation are presented in Table 2. Results of accuracy studies are presented in Table 5. Percent recovery for DEX and DOM by both the methods was found in the range of 99.94% to 102.5 % and 99.88 – 101.08 % and R.S.D. for six determinations of tablet sample, by both the methods, was found to be less than 2.0 indicating the precision of both the methods. Hence, it can be concluded that the developed spectrophotometric method is accurate, precise and can be employed successfully for the estimation of dexrabeprazole sodium and domperidone maleate in bulk and formulation.
CONCLUSION:
The proposed first order derivative spectrophotometric method was found to be simple, economical rapid. The standard deviation and % RSD calculated for the proposed method is within limits, indicating high degree of precision of the method. The results of the recovery studies performed indicate the method to be accurate. Hence, it can be concluded that the developed spectrophotometric method is accurate, precise and can be employed successfully for the estimation of dexrabeprazole sodium and domperidone maleate in bulk and formulation.
ACKNOWLEDGEMENT:
The authors express their gratitude to Emcure Pharmaceutical Limited. Pune, India for Gift samples of pure drugs. Special thanks Smt. Kashibai Navale College of Pharmacy and Dr. S.D. Sawant, Principal of SKNCOP for providing excellent infrastructure facility to carry out this research work.
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Received on 09.03.2011 Modified on 01.04.2011
Accepted on 11.04.2011 © RJPT All right reserved
Research J. Pharm. and Tech. 4(7): July 2011; Page 1086-101089