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ISRN Analytical Chemistry
Volume 2012 (2012), Article ID 401702, 4 pages
http://dx.doi.org/10.5402/2012/401702
Research Article

Simultaneous Estimation of Lafutidine and Domperidone by Ultraviolet Spectroscopy

1Department of Pharmaceutical Analysis, Genba Sopanrao Moze College of Pharmacy, Wagholi, Maharashtra, Pune 412207, India
2Department of Formulation and Development, Alkem Laboratories Ltd., Panvel 410208, India

Received 23 March 2012; Accepted 23 April 2012

Academic Editors: D. J. Fletouris and D. Patra

Copyright © 2012 Kiran Jadhav et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A simple, accurate, and precise method for simultaneous estimation of Lafutidine and Domperidone in combined-dosage form have been described. The method employs formation and solving of simultaneous equations using 279 and 284 nm as two analytical wavelengths. This method allows the simultaneous determination of Lafutidine and Domperidone in concentration ranges employed for this purpose with the standard deviation of <1.0% in the assay of tablet.

1. Introduction

Lafutidine (LAF) is (furan-2-ylmethylsulphinyl)-N-[(Z)-4-[4-(piperidinyl-methyl)-pyridin-2-yl) oxybut 2-enyl] acetamide (Figure 1) [1]. It is freely soluble in methanol, whereas it is practically insoluble in water. It is a second generation histamine H2-receptor antagonist used as an antiulcerative agent [2]. Domperidone (DOP) is chemically 5-chloro-1-[1-[3-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl) propyl]-piperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one (Figure 2) used as an antiemetic drug [3, 4]. A combination of these drugs, DOP (10 mg) and LAF (10 mg) is available as tablets for clinical practice. This unique combination has comprehensive acid control and prokinetic action which ensures better control and relief from reflux, gastric ulcers, and associated gastrointestinal (GIT) disorders. Many methods like HPLC4,5, HPTLC7, and LCMS9 [59] have been described in the literature for the determination of DOP and LAF individually or in combination with others. However, there is no spectroscopic method reported for the simultaneous determination of these drugs either as active pharmaceutical ingredient or from dosage forms. The present work describes a simple, precise, and accurate simultaneous ultraviolet spectrophotometric method for simultaneous estimation of LAF and DOP in combined dosage forms.

401702.fig.001
Figure 1: Structure of lafutidine.
401702.fig.002
Figure 2: Structure of domperidone.

2. Experimental

2.1. Materials and Methods

UV/Vis double beam spectrophotometer, model-Shimadzu UV 1800 PC with 1 cm quartz cells was used. Standard bulk drug samples of LAF (99.45% pure) and DOP (99.67% pure) were provided as gift samples by Ajanta Pharmaceuticals Ltd, Mumbai, India and Cipla Ltd., Mumbai, India, respectively. The pharmaceutical dosage form used in this study was Lafaxid D tablets with a declared content of 10 mg LAF and 10 mg DOP USP per tablet (Zuventis healthcare Ltd., Mumbai).

2.2. Preparation of Solutions

LAF and DOP standard stock solution (0.5 mg/mL) was prepared by transferring accurately weighed 50 mg portion of each drug in 100 mL volumetric flask, dissolved in 50 mL of methanol and volume was made up with distilled water to give concentration of 500 μg/mL.

2.3. Methodology

Selection of analytical wavelengths was done by taking pure samples of LAF and DOP which were separately dissolved in methanol to give two solutions of 25 and 50 μg/mL, respectively. They were scanned in the wavelength range of 200–400 nm. From the overlain spectra (Figure 3), wavelengths 279 and 284 nm were selected for the formation of simultaneous equations. For constructing a calibration curves, two series of different concentrations in range of 10–150 μg/mL for LAF and 5–40 μg/mL for DOP were prepared from stock solutions. The calibration curves were plotted at 279 and 284 nm. The absorptivities (A1%, 1 cm) of both the drugs at both the wavelengths were determined. These calculated values were the mean of five independent determinations. The absorbance and absorptivities values at the particular wavelengths were calculated and substituted in the Cramer’s rule to obtain the concentrations: 𝐴𝐶𝑥=2𝑎𝑦1𝐴1𝑎𝑦2𝑎𝑥2𝑎𝑦1𝑎𝑥1𝑎𝑦2,𝐴𝐶𝑦=1𝑎𝑥2𝐴2𝑎𝑥1𝑎𝑥2𝑎𝑦1𝑎𝑥1𝑎𝑦2.(1)𝐶𝑥 and 𝐶𝑦 are concentration of LAF hydrochloride and DOP, respectively, (in gram/100 mL) in sample solution. The validity of formed equations was checked by preparing five mixed standards, measuring their absorbances at respective wavelengths and comparing these with the absorbances calculated using above formed equations.

401702.fig.003
Figure 3: Overlain spectra of LAF and DOP (400–200 nm).
2.4. Estimation from Tablets

The pharmaceutical dosage form used in this study was Lafaxid D tablets with a declared content of 10 mg LAF and 10 mg DOP USP per tablet (Zuventis healthcare Ltd., Mumbai).

Twenty tablets of brand Lafaxid D tablets were weighed and finely powdered. Accurately weighed tablet powder equivalent to 10 mg was taken in 100 mL volumetric flask. 20 mL of methanol was added and sonicated for 5 min. The volume was made to mark with distilled water. Aliquot portion of this solution was further diluted to achieve final concentration of 25 μg/mL for LAF and DOP. The absorbances were noted at respective wavelengths. The concentration of each drug in tablet formulation was determined using above methods.

3. Result and Discussion

The overlain spectra of LAF and DOP in the concentration ratio of 1 : 1 showed that the peaks are resolved, thus satisfactory criteria for obtaining maximum precision based on absorbance ratios. The criteria being the ratios (𝐴2𝐴1/𝑎𝑋2𝑎𝑋1) for drug Y and (𝑎𝑌2𝑎𝑌1/𝐴1𝐴2) for drug X should lie outside the range of 0.1–2.0 where 𝐴1 and 𝐴2 represent absorbance of tablet solution at 𝜆1 and 𝜆2, 𝑎𝑋1 and 𝑎𝑋2 represent absorptivities of X at 𝜆1 and 𝜆2, and 𝑎𝑌1 and 𝑎𝑌2 denote absorptivities of Y at 𝜆1 and 𝜆2, respectively. In the present contest, the above criteria was found to be satisfing for LAF (X) and DOP (Y) where 𝜆1 is 279 nm and 𝜆2 is 284 nm. In overlain spectra, LAF shows two distinct peaks, one at around 230 and the other at 279 nm. The peak at 279 nm was found to be prominent hence for simultaneous equations method; the peak was used for determination of LAF. Since only one prominent peak exists for DOP at 284 nm, the same was used for its determination. Absorbance was determined at the both wavelengths.

Calibration curves were plotted and regression analysis was carried out. The linearity range of LAF was found to be 10–100 μg/mL and for DOP 5–40 μg/mL. The absorpitivity was then calculated and substituted in (1) along with absorbance values to obtain concentration of drugs.

3.1. Validation

LOD and LOQ were calculated, in accordance with ICH guidelines, as 3.3r/S and 10r/S, respectively, where 𝑟 is the standard deviation of the response (y-intercept) and 𝑆 is the slope of the calibration plot. To study intraday variation, six mixed standard solutions containing LAF (50 μg/mL) and DOP (50 μg/mL) were prepared and absorbance was taken. All the solutions were analyzed on the same day to record any intraday variation in the results. To study interday variation, analysis of three mixed standard solutions of the same concentration was performed on different days (Table 1).

tab1
Table 1: Determination of precision.
3.2. Recovery Studies

To check the accuracy of the method, recovery was measured by addition of standard drug solution at three different levels (80, 100, and 120%) to preanalyzed sample solution (Table 2).

tab2
Table 2: Determination of accuracy by percentage recovery method.

By observing the validation parameters (Table 3), the method was found to be specific, accurate, precise, repeatable, and reproducible. Hence, this method can be employed for routine analysis of tablet for assay as well as dissolution testing.

tab3
Table 3: Summary of validation parameters.

4. Conclusion

Simple, new, simultaneous UV spectroscopic method was developed and validated. The proposed method is accurate, precise, reproducible, and economical and can be successfully used for routine analysis of simultaneous estimation of lafutidine and domperidone.

Acknowledgment

The authors would like to thank Shri Rambhau Moze, Honorable President of Genba Sopanrao Moze Trust for his kind support.

References

  1. W. D. Chen, Y. Liang, H. Li et al., “Simple, sensitive and rapid LC-ESI-MS method for the quantitation of lafutidine in human plasma—application to pharmacokinetic studies,” Journal of Pharmaceutical and Biomedical Analysis, vol. 41, no. 1, pp. 256–260, 2006. View at Publisher · View at Google Scholar · View at Scopus
  2. Y. Akiba and J. D. Kaunitz, “Lafutidine, a protective H2 receptor antagonist, enhances mucosal defense in rat esophagus,” Digestive Diseases and Sciences, vol. 55, no. 11, pp. 3063–3069, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. I. L. Swann, E. N. Thompson, and K. Qureshi, “Domperidone or metoclopramide in preventing chemotherapeutically induced nausea and vomiting,” BMJ, vol. 2, no. 6199, article 118, 1979. View at Scopus
  4. A. Karthik, G. Subramanian, A. Ranjith Kumar, and N. Udupa, “Simultaneous estimation of paracetamol and domperidone in tablets by reverse phase HPLC method,” Indian Journal of Pharmaceutical Sciences, vol. 69, no. 1, pp. 142–144, 2007. View at Scopus
  5. M. Kobylińska and K. Kobylińska, “High-performance liquid chromatographic analysis for the determination of domperidone in human plasma,” Journal of Chromatography B, vol. 744, no. 1, pp. 207–212, 2000. View at Publisher · View at Google Scholar · View at Scopus
  6. M. Cignitti, M. C. Ramusino, and L. Rufini, “UV spectroscopic study and conformational analysis of domperidone,” Journal of Molecular Structure, vol. 350, no. 1, pp. 43–47, 1995. View at Scopus
  7. B. H. Patel, B. N. Suhagia, M. M. Patel, and J. R. Patel, “HPTLC determination of rabeprazole and domperidone in capsules and its validation,” Journal of Chromatographic Science, vol. 46, no. 4, pp. 304–307, 2008. View at Scopus
  8. Y. Xing and H. Fa, “Determination of lafutidine and its tablets by HPLC,” Journal of Zhejiang University. Science. B, vol. 6, no. 1, pp. 74–78, 2005.
  9. C. X. Pan, X. Z. Xu, H. M. He, X. J. Cai, and X. J. Zhang, “Separation and identification of cis and trans isomers of 2-butene-1,4-diol and lafutidine by HPLC and LC-MS,” Pharmaceutical Journal, vol. 6, 2003.