DETERMINATION OF LAFUTIDINE THROUGH OXIDATIVE COUPLING REACTION IN BULK SAMPLE AND DOSAGE FORMS- A NEW APPROACH
HTML Full TextDETERMINATION 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.
Keywords: |
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
S.No | Medium | Absorbance |
1 | Acidic | 0.434 |
2 | Basic | 0.464 |
3 | Neutral | 0.536 |
Different orders of additions were carried with Drug, MBTH and FeCl3. 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
Volume of NaIO4 (0.2%) | Absorbance |
0.5 ml | 0.387 |
1.0 ml | 0.628 |
1.5 ml | 0.594 |
2.0 ml | 0.603 |
2.5 ml | 0.573 |
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
Volume of MBTH (0.2%) | Absorbance |
0.5 ml | 0.419 |
1.0 ml | 0.563 |
1.5 ml | 0.601 |
2.0 ml | 0.635 |
2.5 ml | 0.559 |
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
Parameter | Value |
Maximum absorption | 630 nm |
Colour of the product | Green |
Molar absorptivity(L.mol-1 cm-1) | 2.51x104 |
Sandell’s sensitivity ( µg/cm2) | 0.01719 |
Beer’s law limit( µg/ml) | 1-18 |
Regression equation(Y=a+bX) slope(b)Intercept(a)Y-absorbance and X-concentration in µg/ml | 0.056660.025 |
Standard Deviation | 0.37782 |
Limit of Detection (μg.mL-1) | 0.22 |
Limit of Quantitation (μg.mL-1) | 0.66 |
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.
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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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Article Information
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2626-30
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English
Ijpsr
M. Srinivasa Reddy and B. Hari Babu *
Department of Chemistry, Acharya Nagarjuna University, Guntur, A.P., India
dr.b.haribabu@gmail.com
01 November, 2014
19 December, 2014
15 February, 2015
10.13040/IJPSR.0975-8232.6(6).2626-30
01 June, 2015