DETERMINATION OF LAFUTIDINE THROUGH OXIDATIVE COUPLING REACTION IN BULK SAMPLE AND DOSAGE FORMS- A NEW APPROACH

DETERMINATION OF LAFUTIDINE THROUGH OXIDATIVE COUPLING REACTION IN BULK SAMPLE AND DOSAGE FORMS- A NEW APPROACH

Srinivasa Reddy ¹ and B. Hari Babu ^*2

Department of Chemistry ¹, K.R.K. Govt. Degree College, Addanki, Prakasam (Dist), A.P., India.

Department of Chemistry ², Acharya Nagarjuna University, Guntur-522510, A.P., India

ABSTRACT: A simple, sensitive, highly accurate method has been developed for the determination of Lafutidine in bulk sample and dosage forms. This method is based on the oxidative coupling reaction of drug with 3-methyl-2-benzothialinone hydrazine hydrochloride (MBTH) reagent in the presence of ferric chloride to form green colored chromogen exhibiting maximum absorption at 630 nm. Beer’s law was obeyed and quantitative results were obtained in the range of 1-18µg/mL. The results of the analysis for the methods have been validated statistically.

Lafutidine, visible spectrophotometry, MBTH, Ferric Chloride, oxidative coupling

INTRODUCTION: Lafutidine, a newly developed histamine H(2)-receptor antagonist, inhibits gastric acid secretion. It is currently marketed in Japan, China and India. It is not only suppresses gastric acid secretion, but also possesses cytoprotective properties. After oral administration, Lafutidine is quickly absorbed in the GIT. The plasma protein binding ability of Lafutidine is 88%. The drug is predominantly metabolized via CYP2D6 and CYP3A4 enzymes.

It decreases inflammation by modulating calcitonin gene-related peptide and vanilloid receptors. It is also found to stimulate mucin biosynthesis and promote the restitution of damaged mucosa. Lafutidine is mostly excreted in urine as drug metabolites and as unchanged drug, to some extent

IUPAC name of Lafutidine is 2-[(2-furylmethyl)sulfinyl] – N- ((2Z)-4-{[4-(piperidin-1-ylmethyl) pyridine - 2 - yl] oxy}but – 2 – en - 1 - yl) acetamide  Fig. 1.

FIG. 1: STRUCTURE OF LAFUTIDINE

Lafutidine is a white to pale yellow crystalline powder. It is freely soluble in methanol, whereas it is practically insoluble in water. But Lafutidine is soluble and stable ¹ in acidic medium. A survey on literature revealed that few UV-Spectrophotometric ^2-7, Spectrofluorimetric ⁸, High performance liquid chromatographic ^9-18 and other ¹⁹ methods were available for the estimation of the titled drug. However, according to the knowledge of the author no visible spectrophotometric method was reported so far. So, in the present investigation it was aimed to develop a novel visible spectrophotometric method with good accuracy, simplicity, precision and economically viable for the determination of Lafutidine in bulk and tablet dosage forms.

MATERIALS AND METHOD:

Instrumentation:

A UV-Visible spectrophotometer (Make-Analytical Technologies, model- Spectro-2080) with 10mm matched quartz cells was used. All weighing were done on electronic balance.

Reagents and Chemicals:

All the chemicals and reagents used were of analytical grade and only freshly prepared solutions were used in the present work.

MBTH Solution:

Prepared by dissolving 0.2 g of MBTH in 100 mL distilled water.

FeCl₃ Solution:

Prepared by dissolving 0.7g of ferric chloride in100 mL 0.5N Hydrochloric acid solution.

Standard Stock Solution of Lafutidine:

100 mg of Lafutidine was accurately weighed and transferred into a standard100mL volumetric flask and dissolved in 25mL of 0.1N Hydrochloric acid by shaking manually for 2 min. The volume was made up to the mark with the same solution. The concentration of the solution is 1000 µg.mL^-1.

Working Standard Solution of Lafutidine:

10 mL of standard stock solution was transferred into another 100 mL volumetric flask and made it up to the mark with 0.1N Hydrochloric acid to get 100 μg.mL^-1 solution.

Recommended Procedure:

Aliquots of working standard of Lafutidine solution (0.3,0.6,0.9,1.2,1.5 and 1.8mL) were added to a series of 10mL volumetric flasks. After that 2.0 mL of 0.2% MBTH solution followed by 1.0ml of 0.7% FeCl₃ were added to each flask and kept aside for 30 min. The volume was made upto the mark with distilled water. The absorbance was measured at 630nm against similar reagent blank. The amount of Lafutidine was determined from the calibration curve (Fig.3).

Procedure for the Assay of Lafutidine in Pharmaceutical Dosage Forms:

Twenty tablets were weighed accurately and reduced to fine powder, Out of which drug equivalent to 100 mg of Lafutidine taken in a 100ml volumetric flask and dissolved in 25mL of 0.1N Hydrochloric acid by shaking manually for 2 min. The  volume  was  made  up  with  the same solution  up  to  the  mark, filtered by  using  Whattmann-42 filter paper. The filtrate was quantitatively diluted with 0.1N Hydrochloric acid to produce concentrations in the linear range of the assay of Lafutidin

RESULTS AND DISCUSSIONS:

The proposed method for the determination of Lafutidine through Oxidative Coupling Reaction in Bulk Sample and Dosage Forms was found to be accurate, simple and rapid. Lafutidine possesses different functional groups such as secondary amine, ketone and ether of varied reactivity. The method is based on the oxidative coupling reaction with MBTH in the presence of FeCl₃. Under  the  reaction  conditions, MBTH  loses  two  electrons  and  one  proton  on oxidation,  forming  the  electrophilic  intermediate which  can be substituted on Lafutidine to form a green coloured product. Probable mechanism of the reaction was given in the scheme (Fig 2).

FIG.2: MECHANISM OF THE REACTION

The optimization of reaction conditions like time required for maximum colour development, effect of buffer, effect of concentration of ferric chloride and MBTH and effect of temperature were studied. Time scan was carried out to find the time required for maximum colour development.

It was noticed that a minimum of 25 minutes required for maximum colour development (Fig.3). It was also observed that the colour is stable for more than 5 hours.

FIG.3: TIME SCAN: PROGRESS OF REACTION OF LAFUTIDINE WITH MBTH-FeCl₃

Colour development of drug with reagents (MBTH &FeCl₃) was carried out in acidic, basic and neutral media. But it was found that neutral medium has more absorbance compared to the other two shown in Table 1.

TABLE 1: EFFECT OF BUFFER ON COLOUR DEVELOPMENT

Different orders of additions were carried with Drug, MBTH and FeCl_3. But, not much variation in absorbance was observed. It was found that the order of addition of Drug_, MBTH and FeCl₃ gave good results. Colour development experiment was carried out by changing the concentration of FeCl₃ from 0.5mL to 2.5mL. It was found that 1.0mL of FeCl₃ is optimum concentration shown in Table 2.

TABLE 2: VARIATION OF ABSORBANCE w.r.t FeCl₃

Colour development experiment was carried out by changing the concentration of MBTH from 0.5mL to 2.5mL. It was found that 2.0mL of MBTH is optimum concentration shown in Table 3.

TABLE 3: VARIATION OF ABSORBANCE w.r.t MBTH

 Absorption spectra:

The absorption spectra of Lafutidine drug with 3-methyl-2-benzothialinonehydrazone hydrochloride (MBTH) in the presence of Ferric Chloride to form colored chromogen exhibiting maximum absorption at 630 nm. The reagent blank exhibited negligible absorbance despite having the same wavelength in the same region. The maximum absorption, progress of reaction of lafutidine and Beer’s law validity were shown in Fig. 4-6.

FIG.4: ABSORPTION SPECTRUM OF LAFUTIDINE WITH MBTH-FeCl₃

The analytical parameters obtained with the optimization experiments were given in Table 4.

FIG.5: TIME SCAN: PROGRESS OF REACTION OF LAFUTIDINE WITH MBTH-FeCl₃

FIG.6: BEER'S LAW PLOT OF LAFUTIDINE WITH MBTH-FeCl₃

TABLE 4: ANALYTICAL PARAMETERS OBTAINED WITH OPTIMIZATION

CONCLUSION: The proposed method was found to be simple, selective and sensitive. The statistical parameters clearly indicate the reproducibility and accuracy of the methods. Analysis of the authentic samples containing Lafutidine showed no interference from the common excipients. Hence, the method could be considered for the determination of Lafutidine in the quality control laboratories.

REFERENCES:

1. Jadhav K.V, Dhamecha D.L, Asnani G.P, Patil P.R, and Patil M.B, "Stability-indicating stress degradation studies of lafutidine using UV   spectrophotometric method." Pharmaceutical Methods, 2013, 4(1): 21-25.
2. Kiran Jadhav, Dinesh Dhamecha, Amol Tate, Harshad Tambe, and Mrityunjaya B. Patil. "Application of UV spectrophotometric method for easy and rapid estimation of lafutidine in bulk and pharmaceutical formulation." Pharmaceutical methods, 2011, 2(4): 264-267.
3. Jadhav, Kiran, Dhamecha D. L, Ghadlinge S. V, Asnani G. P, and Patil M. B. "Simultaneous estimation of lafutidine and domperidone by ultraviolet spectroscopy."ISRN Analytical Chemistry, 2012, no. Article ID 401702, 1-5, 2012.
4. Moon, Swagati A., Subhash G. Chate, Bhanudas S. Kuchekar, Patil S. A, Sonali L. Patil, and Bharat D. Pagare."Spectrophotometric simultaneous determination of lafutidine and domperidone in combined tablet dosage form by absorbance corrected method and first order derivative method." Der Pharma Chemica, 2012, 4(3): 930-934.
5. Parekh Ravishkumar, Patel Pinkal R.H, Patel Chinmay D, Patel Krupali S, and Patel Hardik N. "Development and Validation of UV Spectrophotometric method for estimation of Lafutidine in bulk and Pharmaceutical dosage form." Int J Drug Develop Res, 2012, 4(1): 325-29.
6. Dave, Vidhi S., and Mandev B. Patel. "Method Development and Validation Of Difference UV Spectrophotometric Estimation Of Lafutidine In Bulk And Pharmaceutical Dosage Form" International Journal of Pharmacy and Pharmaceutical Sciences, 2012, 4(4): 284-287.
7. Rana, Shefali, Jigar Pandya, Sagar Solanki, and Mandev Patel. "Development and Validation of Spectrophotometric method for Simultaneous estimation of Lafutidine and Domperidone in combined dosage form by area under curve method." Int J Drug Develop Res, 2012, 4(1): 257-62.
8. Patel, Kinjal M, Kunti Shah, and Samir Patel. "Spectrofluorimetric Method for Determination of Lafutidine in Pharmaceutical Dosage Form."International Journal of Pharmacy & Pharmaceutical Sciences, 2013, 5, (3): 902-904.
9. Lunn, George. HPLC methods for recently approved pharmaceuticals, 2005, John Wiley & Sons, p.p. 334.
10. Sumithra M, Shanmuga Sundaram P, and. Srinivasulu K. "Analytical Method Development and Validation of Lafutidine in Tablet dosage form by RP-HPLC." Int J Chem Tech Res, 2011, 3(3):  1403-1407.
11. Dipanjan, Ray Chaudhury, Chakraborty Mithun, Chakraborty Susanto, and Saha Nandita. "Simultaneous determination of Lafutidine and Domperidone in Tablet dosage form by HPLC." International Journal of Research Article Pharmaceutical Innovations, 2012, 2(6): 1-11.
12. Jagadeeswaran M, Gopal N, Jayakar B, and Sivakumar T. "Simultaneous Determination of Lafutadine and Domperidone in Capsule by High Performance Liquid Chromatography."Global Journal of Pharmacology, 2012, 6(2): 60-64.
13. Moon, Swagati A., Korhale R. V, Jadhav S. L, Biradar N. S, Puri D. C, and Shrikant A. Karande Patil."Development and Validation of RP-HPLC Method for Simultaneous Estimation of Lafutidine and Domperidone Maleate in Tablet Dosage Form."Asian Journal of Research in Chemistry, 2012, 5(6): 781-786.
14. Santhosha B, Ravindranath, A and C. Sundari. "Stability indicating RP-HPLC method for the simultaneous estimation of Domperidone and Lafutidine in bulk and the pharmaceutical dosage form." International Journal of Pharmacy and Pharmaceutical Sciences, 2012, 4(4): 589-594.
15. Antala, Hiren. D: Development and Validation of RP-HPLC Method for the Simultaneous Estimation of Lafutidine and Rabeprazole Sodium in Combined Dosage Form." Inventi Rapid: Pharm Analysis & Quality Assurance, 2013; 5(4): 128-135.
16. Moorkoth, Sudheer, Sunny Kumar, Aravinda Pai, and Venkatesh B. Kamath."Stability Indicating Analytical Method Development and Validation of Lafutidine in Tablet Dosage form by RP-HPLC." MintageJournal of Pharmaceutical & Medical Sciences, 2013; 2(1): 18-21.
17. Prajapati, Nitin D, Atul A. Shirkhedkar, and Sanjay J. Surana. "Stability-indicating reversed-phase high-performance thin-layer chromatography/densitometry estimation of lafutidine in bulk and tablets." Chemical Industry and Chemical Engineering Quarterly, 2013, 19(2): 213-219.
18. Ghode, Prashant D, and Sunil P. Pawar. "Stability Indicating HPLC Method Development and Validation for the Simultaneous Determination of Lafutidine & Domperidone in its dosage forms.” World Journal of Pharmacy and Pharmaceutical Sciences, 2014, 3(9): 896-913.
19. Rajan, Rele V, Pankaj J. Gurav, and SawantSwapnil. A. "A Validated Non-aqueous Potentiometric Titration Method for the Quantitative Determination of Lafutadine from Pharmaceutical Preparation." Asian Journal of Research in Chemistry, 2012, 5(6): 722-724
    

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How to cite this article:

Reddy MS and Babu BH: Determination of Lafutidine through Oxidative Coupling Reaction in Bulk Sample and Dosage Forms- A New Approach. Int J Pharm Sci Res 2015; 6(6): 2626-30.doi: 10.13040/IJPSR.0975-8232.6(6).2626-30.

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