INTRODUCTION:

Lafutadine is H₂ rceptor antagonists. Its chemical name is 2[2(-furylmethyl)sulfuryl]-N-[2Z-4-{4-(piperidinyl1methyl) pyridin-2yl] oxy}but-2en-l-yl) actamide. This drug is not official in any pharmacopoeia. In literature survey only HPLC^1,and spectrophotometric^2-5 methods has been reported for asay of lafutadine. A simple precise, rapid accurate and sensitive non-aqueous potentiometric titration method was developed for quantitative determination of lafutadine from bulk drug and pharmaceutical formulation. The developed method will useful for pharmaceutical industries and research organizations.

EXPERIMENTAL:

Instrumentation

An potentiometric titrator was used (Veego-Matic) for assay method development and validation. A Shimadzu analytical balance with 0.01 mg was used.

Reagents and chemical

Reference standard of lafutadine was obtained from reputed firm with certificate of analysis. Potassium hydrogen phthalate, perchloric acid and glacial acetic acid of A. R. grade were used.

General procedure

Standardization of 0.1 N perchloric acid

About 0.350 mg of potassium hydrogen phthalate (previously powdered lightly, dried at 120^oC for 2 hours) was weighed accurately into clean and dry titration jar. It was dissolved in 50 ml of glacial acetic acid. About 0.1 ml of crystal violet solution (0.5 % w/v in anhydrous glacial acetic acid ) was added. It was titrated with 0.1 N perchloric acid until violet colour changes to emerald green. Blank determination was performed out for necessary correction. The titration was performed in duplicate.

One ml of 0.1 N HClO₄ is equivalent to 0.2042 gm of potassium hydrogen phthalate (C₈H₅KO₄)

Normality of perchloric acid = --------------------

B.R. x 0.2042

Where, W is weight of potassium hydrogen phthalate in g.

B.R. is burette reading in ml.

Quantitative determination of lafutadine

About 0.100 g. of lafutadine test sample was weighted accurately into a clean and dried titration jar. It was dissolved in 50 ml. of anhydrous glacial acetic acid.

It was titrated with 0.1 N perchloric acid potentiometrically. Blank determination was also carried out for necessary correction.

One ml of 1 N perchloric acid is equivalent to 0.14384 g. of lafutadine

% (Percentage) Lafutadine on the dried basis was calculated as below

B.R. x N x 0.14384 x 100

% Assay = _____________________________

Where, B.R. is burette reading in ml at the potentiometric end point.

N is actual normality of 0.1 N perchloric acid.

W is weight of the sample taken in g.

RESULT AND DISCUSSION:

Determination of lafutadine:

The objective of this work was to determine accurately the content of lafutadine. The assay of lafutadine ( on the dried basis) of various batches of lafutadine test sample was analyzed using the above method. It was in the range of 100.569 % to 101.46 %.

Analytical method validation:

The method precision was checked after analyzing six different preparations of homogeneous test sample of lafutadine. The % RSD of results obtained was found to be 0.4520. It confirms good precision of the method. The results are presented in table 1.

TABLE NO. 1 Method of Precision

Weight of Burette Normality %Assay

lafutadine reading of perchloric

in g. in ml acid

0.100 7.0 0.09991 100.569

0.100 7.05 0.09991 101.315

0.100 7.0 0.09991 100.569

0.100 6.95 0.09991 99.878

0.100 7.0 0.09991 100.56

0.100 7.0 0.09991 100.569

_________________________________________________________Mean 100.578 %; Standard deviation 0.4546; % RSD 0.4520

Linearity :

For the establishment of method linearity ,five different weights of lafutadine test samples corresponding to 20 % , 40 %, 60 % , 80 % and 100 % of the about weight ( 0.100 g.) were taken and analyzed for % (percentage) of lafutadine content. The results are in table 2.

TABLE NO.2 Linearity

Level Weight of Burette reading Normality % Assay

lafutadine ml of perchloric

in g. acid

1. 0.020 1.4 0.09991 100.569

2 0.040 2.8 0.09991 100.569

3 0.060 4.2. 0.09991 100.569

4 0.080 5.65 0.09991 101.46

5 0.100 7.0 0.09991 100.569

Mean 100.747 % Standard deviation 0.3984 % RSD 0.3955

The potentiometric titration was conducted once at each level. Calibration curve was drawn by plotting test sample weight in gram on x axis and titre values on y axis.

The values of correlation coefficient, slope and intercept are given in table 3.

TABLE NO. 3 Regression Values

Correlation coefficient 0.9999

Slope (m) 70.25

Intercept (c) 0.005

Regression equation y = 70.25x - 0.005

Accuracy and recovery:

Accuracy was determined at five different levels i.e., 20 %, 40 % ,60 % ,80 % and 100 % of the nominal concentration. (0.100 g.) The titration was conducted in triplicate at each level and the titre value was recorded. The tire value obtained in linearity study was considered as true value during the calculation of percentage (%) recovery. The percentage recovery is calculated using following equation.

Titre value x 100

Percentage recovery = ---------------------------

True titre value

The percentage range recovery of lafutadine was in 100.338 to 101.16 %. It confirms the accuracy of the proposed method. (Table 4).

TABLE NO 4 Accuracy and Recovery

Level Weight of `Weight of % Assay Mean

Lafutadine Lafutadine % assay

added (g.) found (g.)

1 0.020 0.0211 100.569 101.766

0.020 0.0208 104.161

0.020 0.0211 100.569

2 0.040 0.0402 100.569 101.16

0.040 0.0409 102.365

0.040 0.0402 100.569

3 0.060 0.0603 100.569 100.866

0.060 0.0608 101.46

0.060 0.0603 100.569

4 0.080 0.0804 100.569 100.535

0.080 0.0785 100.467

0.080 0.0811 100.569

5 0.100 0.1005 100.569 100.338

0.100 0.0998 99.878

0.100 0.1018 101.569

Ruggedness:

The ruggedness of the method is defined as degree of reproducibility of results obtained by analysis of lafutadine sample under variety of normal test conditions such as different laboratories, different analysts and different lots of reagents. Quantitative determination of lafutadine was conducted potentiometrically on one laboratory. It was again tested in another laboratory using different instrument by different analyst. The assays obtained in two different laboratories were well in agreement. It proved ruggedness of the proposed method.

CONCLUSION:

The proposed method of non-aqueous potentiometric titration was found to be precise, accurate and rugged. The values of percentage recovery and standard deviation showed sensitivity. The method was completely validated. It showed satisfactory data for all the parameters of validation. Hence it can be applied for routine quality control application.

REFERENCES:

1. M. Sumithra, P. Shanmuga and K. Srinivasulu; A simple, sensitive and rapid reverse phase high performance liquid chromatographic method for the simultaneous estimation of lafutidine in tablet dosage form; International Journal of Chemtech Research. 03(03) ; 2011:1403-1407.

2. Kiran Jadhav, Dinesh Dhamecha, Amol Tate, Harshad Tambe and Mrityunjaya B. Patil; A UV spectrophotometric method for the estimation of lafutidine in bulk and pharmaceutical dosage form; An Addendum to Journal of Young Pharmacist. 02, (04); 2011 :264-267.

3. Prajapati Nitin D., Shirkhedkar Atul A., and Surana Sanjay J.; A new simple, economical and rapid UV spectrometric first order derivative method using ‘Area Under Curve’ (AUC) technique for the estimation of lafutidine in bulk and tablets; Journal of Pharmaceutical Research. 10(04); 2011.

4. Parekh Ravishkumar R., Patel Pinkal H., Patel Chinmay D., Patel Krupali S., amd Patel

Hardik N.; A UV spectrophotometric method for estimation of lafutidine from bulk and pharmaceutical formulation; International Journal of Drug Development and Research. 04 (01);2012 :325-329.

5 G. Usha rani, B. Chadrakant and N.Devanna; Application of UV-spectrophotometric method for easy and rapid estimation of lafutidine in bulk and pharmaceutical formulations; Journal of Pharmacy Research. 05(02);2012 :862-863..

Received on 14.05.2012 Modified on 12.06.2012

Asian J. Research Chem. 5(6): June, 2012; Page 722-724