UV Derivative Spectrophotometric Methods for validation of Esomeprazole

Magnesium tri-hydrate in Bulk and Pharmaceutical Dosage Form

 

Rajan V. Rele.*

Central Research Laboratory, D.G. Ruparel College, Matunga, Mumbai 400016.

 

ABSTRACT:

The objective of the study was to develop simple, accurate, precise and rapid UV first and second order derivative spectrophotometric methods with subsequent validation by using ICH guidelines for the determination of Esomeprazole magnesium tri-hydrate in pharmaceutical dosage form. The proposed first and second order derivative methods involve the measurement of absorbance of drug at 293 nm and 281 nm for the estimation of Esomeprazole magnesium tri-hydrate respectively. The linearity of the proposed methods were found in the concentration range of 4-40 µg /ml (r2= 0.9999) for first order and second order derivative methods and the percentage mean recovery was found to be 99.59 % to 100.69 % respectively. The methods were also statistically validated for its linearity, accuracy and precision. Both intra and inter day variation showed less percentage (%) RSD values indicating high grade of precision of these methods.

 

 

 

INTRODUCTION:

Esomeprazole magnsium tri-hydrate is Chemically, bis (5-methoxy-2-[(S)-[(4-methoxy-3, 5- dimethyl - 2 -pyridinyl ) methyl ]sulfinyl ] - 1-H - enzimidazole - 1 -yl) magnesium trihydrate. Such compound prevents secretion of gastric acid. It is S-isomer of omeprazole. It is a first single optical isomer proton pump inhibitor. It gives better acid control than other inhibitors of racemic proton pump. It produces a favorable pharmacokinetic than omeprazole

 

According to the literature review several methods has been developed for drug, like spectroscopy, methods^1-4 HPLC^5-10. The proposed aim of the study was to develop simple, accurate, specific and precise RP-HPLC method for the estimation of drug in the bulk and pharmaceutical formulation.

 

MATERIALS AND METHODS:

Instrument and reagents:

Spectral scan was made on a Shimadzu UV-spectrophotometer, model 1800 (Shimadzu, Japan) with spectral band width of 0.5 nm with automatic wavelength corrections by using a pair of 10 mm quartz cells. All spectral measurements were done by using UV-Probe 2.42 software. Reference standard of esomeprazole magnesium tri-hydrate was obtained from reputed firm with certificate analysis.

 

Preparation of standard drug solution:

40 mg standard esomeprazole magnesium tri-hydrate was weighed accurately and transferred to a 100 ml volumetric flask and sonicated with 30 ml of methanol for 15 minutes. The volume was made up to the mark with methanol to give a stock solution of concentration 400 μg /ml. From this solution, 10 ml of solution was pipetted out and transferred into 100 ml volumetric flask. The volume was made up to mark with methanol to give a working standard solution of concentration 40 μg/ml.

 

Estimation from tablets:

Twenty tablets were weighed accurately and average weight of each tablet was determined. Powder equivalent to 40 mg of esomeprazole magnesium tri-hydrate was weighed and transferred in 100 ml of volumetric flask. A 30 ml of methanol was added and sonicated for 15 minutes and filtered. The filtrate and washing were diluted up to the mark with methanol to give concentration as 400 μg /ml. Such solution was used for analysis.

 

EXPERIMENTAL:

Method: First and second order derivative methods

For the selection of analytical wavelength, 8 μg/ml solution of Esomeprazole magnesium tri-hydrate was scanned in the spectrum mode from 400 nm to 200 nm by using methanol as blank. The first order derivative spectrum was obtained by using derivative mode by UV probe 2.42 software. From the spectrum, the amplitude of the first order derivative spectrum was measured at 293 nm. and second order derivative at 281.7 nm respectively.

 

Preparation of calibration curves:

Series of solutions containing 4-40 µg/ ml of Esomeprazole magnesium tri-hydrate were used to determine linearity of the proposed method respectively. Solutions were scanned in the spectrum mode and absorbance spectra were converted to first order derivative spectra [Fig. 1(a), 1(b)].

 

 

Fig. 1(a): Overlay spectra of first order derivative of Esomeprazole magnesium tri-hydrate in the concentration range of 4-40 µg/ ml.

 

Fig. 1(b): Overlay spectra of second order derivative of Esomeprazole magnesium tri-hydrate in the concentration range of 4-40 µg/ ml.

 

After observing the overlain first and second order derivative spectra of Esomeprazole magnesium tri-hydrate, wave length selected was 293 nm and 282.7nm respectively, where Esomeprazole magnesium tri-hydrate showed considerable absorbance. The calibration curves were plotted of dA/ dλ against concentrations [Fig. 2 (a),(b)].

 

 

Fig.2 (a): Calibration curve of Esomeprazole magnesium tri-hydrate in the concentration range of 4-40 µg/ml.

 

 

Fig.2 (b): Calibration curve of Esomeprazole magnesium tri-hydrate in the concentration range of 2-10 µg/ml.

Results of the analysis are given in table 1.

Table 1: Values of results of optical and regression of drugs

Parameter	First order	Second order
Detection Wavelength (nm)	293	282.7
Beer Law Limits (µg/ml)	4-40	4-40
Correlation coefficient(r2)	0.9999	0.9999
Regression equation (y=b+ac)
Slope (a)	0.0017	0.0003
Intercept (b)	0.00007	0.00005

 

Estimation from tablets:

Twenty tablets were weighed accurately and average weight of each tablet was determined. Powder equivalent to 40 mg of Esomeprazole magnesium tri-hydrate was weighed and transferred in 100 ml of volumetric flask. A 30 ml of methanol was added and sonicated for 15 minutes and filtered. The filtrate and washing were diluted up to the mark with methanol to give concentration as 400 μg /ml of each drug. Such solution was scanned in the range of 200-400 nm against methanol as blank. The absorbance spectra were converted to first order and second order derivative spectra. Calculations were done as per the equations. The concentrations of Esomeprazole magnesium tri-hydrate present in tablets were calculated by substituting the values of absorbance in linearity equations.

 

(a) For first order derivative method, Y = 0.0017x + 7E-05

(b) For second order derivative method, Y = 0.0003x + 1E-05

 

Method Validation:

These methods were validated according to ICH guidelines.

 

Accuracy:

To ascertain the accuracy of proposed methods, recovery studies were carried out by standard addition method at three different levels Percent recovery for Esomeprazole magnesium tri-hydrate was found in the range of 99.59 % to 100.79 for first order derivative method and 99.30 to 100.69 % for second order derivative respectively. (Table 2. (a) and (b)).

 

Table 2 (a): Statistical evaluation of the data subjected to accuracy for first order derivative method

Level of % recovery	Amount  of sample in µg/ml	Amount Std added in µg/ml	Amount found in µg/ml	% Recovery	Mean % recovery
50%	8	8	16.47059	101.1025	99.87729
	8	8	15.88235	99.26469
	8	8	15.88235	99.26469
100%	8	16	23.88235	99.50979	99.5915
	8	16	23.88235	99.50979
	8	16	23.94118	99.75492
150%	8	24	32.29412	100.9191	100.7966
	8	24	32.23529	100.7353
	8	24	32.23529	100.7353
% R.S.D.				0.765254

 

Table 2 (b): Statistical evaluation of the data subjected to accuracy for second order derivative method

 

Linearity:

The linearity of measurement was evaluated by analyzing different concentration of the standard solutions of Esomeprazole magnesium tri-hydrate in the range of 4-40 µg/ml for first order and second order derivative respectively.

 

Precision:

The method precision was established by carrying out the analysis of tablets powder blend containing 10 mg of Esomeprazole magnesium tri-hydrate. The assay was carried out for the drugs by using proposed analytical method in six replicates. The values of relative standard deviation were well within limits 1.5829 % and 1.7614 % for Esomeprazole magnesium tri-hydrate respectively indicating the sample repeatability of the methods. The results obtained are tabulated in table 3.

 

Table 3: Statistical evaluation of the data subjected to method of precision

Sr. No.	Sample No.	% Assay
		First order derivative method	Second order derivative method
1	1	102.18	97.91
2	2	99.25	102.08
3	3	102.93	97.91
4	4	99.62	97.91
5	5	101.06	100.00
6	6	99.25	97.91
Mean % assay		100.71	98.95
%R.S.D.		1.5829	1.7614

 

Intra-day precision was estimated by assaying tablets powder blend containing 40 mg of Esomeprazole magnesium tri-hydrate . The assay was carried out for the drugs by using proposed analytical method in six replicates. The results were average for statistical evaluation.

 

Inter-day precision was estimated by assaying tablets powder blend containing 40 mg of Esomeprazole magnesium tri-hydrate for three consecutive days (i.e. 1st, 3rd and 5th days). The statistical validation data for intra and inter day precision is summarized in table 4.

 

Table 4: Summary of validation parameter for intra-day and inter-day

Sr. No.	Parameters	First order derivative	Second order derivative
1	Intra-day precision (N=3)amount found ± % R.S.D.	100.45%   1.4528	100.28%    1.2824
2	Inter-day precision (N=3)amount found ± % R.S.D.	99.54   1.1215	99.25%   1.1255

 

Both intra- day and inter-day precision variation found to be less in % RSD values. It indicates high degree of precision of the method.

 

RESULT AND DISCUSSION:

The developed first and second order derivative spectrophotometric methods for determination of esomeprazole magnesium tri-hydrate in tablet formulation was found to be simple and convenient for the routine analysis of drug. The proposed method is accurate, precise and reproducible. It is confirmed from validation data as given in tables 1 to 4. The % RSD was found to be less than 1, which indicates validity of method. Linearity was observed by linear regression equation method for Esomeprazole magnesium tri-hydrate in different concentration range. The correlation coefficient of these drugs was found to be close to 1.00, indicating good linearity figure 2 (a) and 2 (b). The assay results obtained by proposed method is shown in table 2 are in good agreement. Hence proposed method can be used for routine analysis pharmaceutical dosage form. Methods are simple, accurate, precise, reliable, rapid, sensitive, reproducible and economical. It is validate as per ICH guidelines.

 

CONCLUSION:

The proposed methods are simple, precise, accurate and rapid for the determination of Esomeprazole magnesium tri-hydrate pharmaceutical dosage form. The methods do not require any ratio of first and second order derivative. The amplitude of first and second order derivative can be directly used to assay of formulation. This method can be adopted as an alternative to the existing methods. It can be easily and conveniently adopted for routine quality control analysis.

 

ACKNOWLEDGEMENT:

Authors express sincere thanks to the principal of D.G. Ruparel College, Dr. Tushar Desai, for encouragement and providing laboratory facilities.

 

REFERENCES:

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Received on 27.07.2017       Modified on 24.08.2017

Accepted on 12.09.2017      © RJPT All right reserved