PHARMACOKINETIC PROFILE AND INCURRED ESOMEPRAZOLE SAMPLE STABILITY IN PLASMA USING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY - PHOTODIODE ARRAY
Objective: Esomeprazole (ESO) is one of the proton-pump inhibitors and is used to treat gastroesophageal reflux. It is sensitive to low pH, heat,
moisture, and oxidation, which often means that ESO in clinical samples is degraded at the time of storage, affecting analysis results. This study aimed
to analyze the in vivo stability of ESO in subjects’ plasma samples by testing the incurred sample stability (ISS) of ESO in plasma following 7, 14, and
28 days of storage at two concentrations close to Cmax and one concentration in the elimination phase.
Methods: Samples were analyzed using high-performance liquid chromatography with a C18 column with detection at 300 nm using a photodiode
array detector. Lansoprazole was used as an internal standard.
Results: The ESO pharmacokinetics profile in the plasma samples yielded the values of Cmax 704.57–1425.85 ng/mL; tmax is 2.25 h; and AUC0-t is
2444 ng.h/mL. ISS testing of plasma samples values were 6.50%, 5.73%, and 4.57% on first Cmax concentration; 3.55%, 4.84%, and 3.68% on 2nd Cmax
concentration; and 4.04%, 4.80%, and 4.98% on elimination phase concentration.
Conclusion: ISS testing results of plasma samples from six healthy subjects who were administered doses of 40 mg of ESO stored for 28 days showed
that it fulfilled the acceptance criteria (<20%) of the 2011 EMEA Bioanalytical Guidelines with a %diff value in all incurred samples of 6.5%.
Pharmacological Basic of Therapeutics. 11th ed. United States of
America: The McGraw-Hill Companies, Inc.; 2006.
2. Dipiro J, Cecily V, Barbara GW, Terry L. Pharmacotherapy:
A Pathophysiologic Approach. 9th Edition. United States: The McGraw-
Hill Companies Inc.; 2015.
3. Scott L, Dunn C, Mallarkey G, Sharpe M. Esomeprazole. Drugs
4. European Medicines Agency. Guideline on Bioanalytical Method
Validation. London: An Agency of the European Union; 2011.
5. Food and Drug Administration. Bioanalytical Method Validation:
Guidance for Industry. America: U.S. Department of Health and Human
Services, Food and Drug Administration; 2018.
6. Fluhler E, Vazvaei F, Singhal P, Vinck P, Li W, Bhatt J, et al. Repeat
analysis and incurred sample reanalysis: Recommendation for best
practices and harmonization from the global bioanalysis consortium
harmonization team. AAPS J 2014;16:1167-74.
7. Gul W, Sajid S, Hamid F, Bhatti S. Effect of acidic Ph. and heat on
the degradation of omeprazole and esomeprazole. Pharm Innov 2015;
8. European Medicines Agency. Nexium Control. London: An Agency of
the European Union; 2013.
9. Reddy PS, Sait S, Vasudevmurthy G, Vishwanath B, Prasad V,
Reddy SJ. Stability indicating simultaneous estimation of assay method
for naproxen and esomeprazole in pharmaceutical formulations by
RPHPLC. Der Pharm Chem 2011;3:553-64.
10. Iuga C, Boji?? M. Stability study of omeprazole. Farmacia 2010;
11. Nardi R, Masina M, Cioni G, Leandri P, Zuccheri P. Generic equivalent
drugs use in internal and general medicine patients: Distrust, confusion,
lack of certainties or of knowledge? Part 3. Clinical Issues. Ital J Med
12. Tothfalusi L, Endrenyi L. Sample sizes for designing bioequivalence
studies for highly variable drugs. J Pharm Pharm Sci 2012;15:73-84.
The 3rd International Conference on Global Health (ICGH), Universitas Indonesia, Bali, Indonesia 219
Int J App Pharm, Vol 11, Special Issue 1, 2019
Harahap et al.
13. Lowes S, LeLacheur R, Shoup R, Garofolo F, Dumont I, Martinez S,
et al. Recommendations on incurred sample stability (ISS) by GCC.
14. Harahap Y, Baskara E, Harmita H. Method validation of esomeprazole
analysis in human plasma using high performance liquid
chromatography photodiode array. J Young Pharm 2017;9:s24-8.
This work is licensed under a Creative Commons Attribution 4.0 International License.