INTRODUCTION:

The condition referred to as high stomach acid production is treated with esomeprazole. It is typically used to treat gastro-esophageal reflux disease (GORD), a disorder that results in heartburn, indigestion, and persistent acid reflux. Vimovo and Nexium are among the brands. Molecular Weight: 345.4g/mol, Molecular Formula: C₁₇H₁₉N₃O₃S. The Elimination Half Life of Esomeprazole is approximately 1 to 1.5hours. while the bioavailability is between 50 and 90%.^1-3

Fig. 01: Structure of Esomeprazole

IUPAC Name: 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl) methyl] sulfinyl}-1H-benzimidazole. To verify the accuracy, precision, and repeatability of the proposed method, statistical validation was used to the experimental data. Esomeprazole lowers the concentration of stomach acid by inhibiting the activity of certain enzymes in the gastric. ⁴

Esomeprazole's maximal plasma concentration (Cmax) might be attained 1.5 hours after oral administration (Tmax). The amount administered is directly correlated with the esomeprazole Cmax. Esomeprazole has a consistent 97% plasma protein binding rate in the concentration range of 2 to 10µg/L.⁵ The liver's cytochrome P450 (CYP) enzyme system breaks it down. Approximately 80% of drugs taken orally are eliminated through the urine, with the remainder inactive metabolites ending up in the feces.

There are several clinical conditions related to stomach issues for which esomeprazole is recommended. ^(6-10)

MATERIAL AND METHODS:

1. Utilised Equipment:

The UV1800s type twin beam UV/Visible spectrophotometer from Shimadzu was used. Its wavelength precision is 0.3 nm, and its spectral bandwidth is 1 nm (achieved through automatic wavelength adjustment using two quartz cells that are matched by 1 cm). The analysis also made use of the Electronic Balancing type AXE 200 and the extreme Sonicator type 2k811056, both manufactured by Shimadzu.

2. Chemicals:

The Pure API of ESO was obtained from Dr. Reddy's laboratories located in Hyderabad, India. The label claims that 50 mg of esomeprazole is included in this formulation.

Selection of Solvents:

Based on the solubility study 1M Urea was selected as the solvent for dissolving the Esomeprazole.

1M Urea preparation:

250ml of water should be used to dilute 15g of urea.

ESO Stock Solution:

To make the stock solution, 10 mg of esomeprazole were precisely weighed, and dissolved in 10 ml of 1M urea into 10ml volumetric flask using ultrasonication for approximately 10 minutes. To get the medicine solution up to the necessary 1000 parts per million concentrations, urea was added.

ESO Working Standard Solution:

Using a pipet, transfer 1 ml to a 10 ml volumetric flask, by using 1M Urea and the concentration was found to be 100ppm. The beer's law was seen in a number of dilutions carried out in the 2–10 µg/ml range.

The dilutions 2, 4, 6, 8, and 10 µg/ml are employed.

Preparation of sample stock solution

A mortar and pestle were used to weigh, smash, and combine ten esomeprazole tablets into a fine powder. Each pill contains 40 milligrams of esomeprazole. One kilogram of powder (0.22 grammes) was added to a 10-milliliter volumetric flask. One milligram of urea made up the volume. The medication solution was filtered using filter paper.

Fig. 02: It shows the UV spectra of esomeprazole (in 1M Urea for determination of λmax)

Method validation:

The robustness, accuracy, precision, and linearity of the procedure were all evaluated.

Linearity:

The recommended techniques produced linear relationships with varying medication concentrations. Plotting the acquired reaction against concentration was done. Absorbance Vs concentration as shown in (Fig.03). The linearity range, where Beers law was followed, was determined to be 2–10µg/ml. The absorbance was measured at 298nm. The regression data are in Table 02.

Acceptance Standards:

1. A linearity regression coefficient greater than 0.999 is required.

2. The appropriate range for the % Y intercept is ±2.0%.

Table 01: Parameters of ESO

Parameters	Value for ESO
Beer’s Law (µg/ml) Limit	2-10 µg/ml
(r²) Correlation Coefficient	0.9983
Regression Equation
Slope	0.0458
Intercept	0.0366

Precision:

Studies conducted within a day proved it. Six times a day, the same concentration solution was analyzed intraday, and the percentage RSD was computed. The %SD and %RSD data are in Table 03.

Acceptance Criteria:

1. Six replicates of standard solutions should have an RSD absorbance at 298nm of less than 2.0%.

Accuracy:

Three replicates of the test were run at each of the three concentration levels - 50%, 100%, and 150%. To achieve 50%, 2ml of a 4ppm sample solution is added to 2ml of standard esomeprazole solution at a concentration of 2ppm. To achieve 100%, 2 milliliters of 4ppm standard solution are spiked with 2 milliliters of 4ppm sample solution. To achieve 150%, 2ml of 4ppm sample solution is added to 2ml of 6ppm standard esomeprazole solution. The absorbance was measured at 298nm for each of these concentrations, and the percentage was computed using the formula below.

Observed concentration

Percentage Accuracy (%) = -----------------------×100

Nominal concentration

The good % R recorded in Table 4, confirms excellent accuracy.

Robustness:

The method's robustness was assessed at a concentration of 6µg/ml of esomeprazole. Minor adjustments were made to the wavelength at which aliquots from a homogeneous ± 1 λmax wavelength were analyzed, and each method was repeated. The reaction remained mostly unaltered, indicating that the process was robust.

RSD% was kept under 2. The data are in Table 05.

RESULT AND DISCUSSION:

Method Validation:

The suggested spectrophotometric methods were validated inconsistently with the ICH guidelines.

Table 02: Linearity of esomeprazole

Concentration (µg/ml)	Absorbance(nm)
2	0.051
4	0.156
6	0.235
8	0.325
10	0.425

Fig. 03: It shows the Standard Calibration curve for (Esomeprazole)

Table 03: Precision

S. No	Absorbance (nm)
1	0.421
2	0.422
3	0.425
4	0.422
5	0.427
6	0.425
AVG	0.42366
SD	0.00233
RSD%	0.55187

Derivatives:

Fig. 04: It shows the Linearity Overlay of Esomeprazole.

Fig. 05: It shows a zero-order overlay of Esomeprazole.

Fig. 06: It shows the first-order overlay of Esomeprazole.

Analytical Greenness Tool:

Fig. 07: Analytical Greenness result

Regarding the impact on the environment, a lower number indicated areas that could use improvement, and a higher value nearer one suggested using a greener method.

The AGREE software program evaluated the greenness of UV Spectrophotometric method based on the values of (GAC) Green Analytical Chemistry. A procedure or method is deemed ecologically friendly and compliant with green analytical chemistry principles when its value is 0.64. A score higher than 0.6 denotes a high level of observance to the principles of GAC, which include eliminating or minimizing the use of harmful chemicals, cutting left-over output, maximizing energy efficiency, and refining aspects pertaining to well-being and protection.

DISCUSSION:

Relative standard deviation (%RSD) was used to express the developed method's precision. These outcomes demonstrate how repeatable the test is. It was discovered that the %RSD values were less than 2(Table 03). Robustness Six times at ±1 λmax, the solutions are measured at with the same concentration. (Table 05). A strong linear association was evident in the linear regression data for the calibration curves for esomeprazole with the concentration range of 2–10µgm/ml. It was discovered that Y=0.0458x-0.0366 (r2=0.9983) is the linear regression equation (Table 02)(Fig-o3). The results of recovery shows % amount was in between 98% and 99.2%, and the % RSD>2.

Table 04: Accuracy

CONC	Drug sample	Drug product	% Recovery
	2ppm	4ppm	101.9
50%	2ppm	4ppm	101.2
H	2ppm	4ppm	101.9
% Mean			101.7
	4ppm	4ppm	98.0
100%	4ppm	4ppm	101.6
	4ppm	4ppm	100.8
% Mean			100.1
	6ppm	4ppm	101.3
150%	6ppm	4ppm	100.3
	6ppm	4ppm	98.1
% Mean			99.79

A quick, accurate, repeatable, and user-friendly UV-Spectrophotometric approach was created by ICH Guidelines to estimate esomeprazole in bulk and its medicinal dosage forms in tablets. The created approaches were found to have the highest level of greenness when the greenness evaluation was used. With little sample preparation, these techniques were effectively used for ESZ assessment and routine quality control analysis.

Table 05: Robustness

SI No	Absorbance 297nm	Absorbance 299nm
1	0.406	0.422
2	0.407	0.422
3	0.412	0.420
4	0.410	0.428
5	0.406	0.424
6	0.410	0.426
AVG	0.4085	0.4236
SD	0.00251	0.00294
RSD%	0.6144	0.6948

POTENTIAL CONFLICTS OF INTEREST:

The authors unanimously agree that this work should be published in this journal and have no conflicts of interest.

AUTHOR CONTRIBUTION:

Author SR is the supervisor of the work designed for the study and the protocol. Author MN finished the experimental study and statistical analysis, wrote the first draft, and managed literature searches. All authors agreed with the final manuscript.

ACKNOWLEDGMENT:

I thank to Dr. Reddy’s Laboratories for the gift sample and Sarojini Naidu Vanitha Pharmacy Maha Vidyalaya for their unwavering support throughout this scientific study effort.

LIST OF ABBREVIATIONS:

ESO: Esomeprazole, ICH: Harmonization International Conference, SD: for standard deviation, RSD: for relative standard deviation, UV: Ultraviolet, AGREE: Analytical Greenness Evaluation.

REFERENCE:

1. Jamakhandi CM, Godambe RD, Kumbhar PS. Development of Spectrophotometric and fluorometric methods for estimation of darunavir using the QbD Approach. Int. J of Current Pharmaceutical Research. 2017; 10(1): 13-19.

2. Mohammad AS et al. Optimization of UV Spectrophotometric Method for the estimation of Darunavir in Bulk Drugs and Tablet Formulation. International Journal of Pharmaceutical Sciences and Nanotechnology. 2016; 9(4): 3345-3348

3. Patel PS. Development and validation of UV- spectrophotometric and RP-HPLC methods for estimation of luliconazole in bulk and gel formulation. World Journal of Pharmacy and Pharmaceutical Sciences. 2019; 8(7): 709-729.

4. Varsha Tegeli, Avinash Birajdar, Varsha Tegeli, Avinash Birajdar. UV Spectrophotometric Method Development and Validation of Darunavir in Bluk and Solid Dosage Form. Research Journal of Pharmacy and Technology. 2021:14(6): 3262-4

5. R. Swetha Sri, S. Jaya Sri, M. Sumakanth. Quantitative Estimation of Vanillin content in various brands of Vanilla Flavored Custard Powder by Conductometry. Research Journal of Science and Technology. 2024; 16(1): 6-10.

6. Raj, P., Rao, R., Mukherjee, P.B., Sarvanan, V.S., Natesan, Gopal, Kalyankar, Tukaram and Shivakumar, T. UV-Spectrophotometric determination of esomeprazole in tablet dosage forms. Asian Journal of Chemistry. 2007; 3250-2

7. Syeda Kulsum, Ayesha Naz, Abdul Rehman, Abdul Bari, Mohammed Salman, Shayestha Jabeena and Samreen Akhter. Analytical Method Development and Validation for Simultaneous Estimation of Naproxen and Esomeprazole in Pharmaceutical Dosage Forms. Journal of Pharmaceutical Research International. 2022; 34(51B): 46-50.

8. M. Mukkanti Eswarudu, A. Lakshmana Rao, K. Vijay. Bioanalytical RP-HPLC Method for Simultaneous Quantification of Rivaroxaban and Ticagrelor in Spiked Human PlasmaL: Validation and Stability. Research Journal of Pharmacy and Technology. 2023; 16(6): 2741-6

9. Girishchandra R. Mandake, Indrajit S. Patil, Omkar A Patil, Manoj M. Nitalikar, Shriniwas K Mohite. UV Spectroscopy Analysis and Degradation Study of Rivaroxaban. Asian J. Res. Pharm. Sci. 2018; 8(2): 57-60

10. Arpitha Sunny, C. Sreedhar, T. Srinivas Rao, Akkama. H.G, Asmita Mahapatra. Development of New Analytical Method and Validation for Quantitation of Estimation of Rivaroxaban in Formulation and Bulk Drug. IJSRE. 2017; 5(5): 6469-6478

11. Hetal Jebaliya, Batuk Dabhi, Madhavi Patel, Yashwantsinh Jadeja, and Anamik Shah. Stress Study and Estimation of a Potent Anticoagulant Drug Rivaroxaban by a Validated HPLC Method: Technology Transfer to UPLC. JCPR. 2015; 7(10): 65-74.

Received on 14.03.2024 Modified on 04.04.2024

Asian J. Pharm. Tech. 2024; 14(2):123-127.

DOI: 10.52711/2231-5713.2024.00022