hypertension, valsartan, atenolol, high-performance liquid chromatography, in vitro bioequivalence, dissolution


Background. The urgent issue of hypertension is determined by its high population incidence, significant burden of the disease, risk of disability and impact on life expectancy. Rational combinations of drugs of different pharmacological groups in case of ineffectiveness of monotherapy to achieve the clinical effect of pharmacotherapy are clearly recommended in the world and national recommendations for diagnosis and treatment of hypertension. Therefore, innovative pharmaceutical development of a combination of antihypertensive drugs and creation of domestic drugs with antihypertensive action is an urgent task of contemporary pharmacy.

Objective. The aim of this study was to perform the quality control measurements and evaluation of dissolution tests for different brands of valsartan and atenolol tablets available in Ukraine.

Methods. The concentrations of valsartan and atenolol in samples (drug content and dissolution study) were determined by the proposed HPLC method.

Results. The results of the tests conducted for evaluation of the tablets were found to be in acceptable limits for all the selected brands. The correlation coefficient (R2) was 0.9991 and the regression equation was y=61.39x+0.3117. It has been established that the equivalence of dissolution profiles for all recommended dissolution media is observed (рН 1.2, 4.5, and 6.8) for the studied drugs. In all three dissolution media, the release rates of valsartan and atenolol of all dosage forms are more than 85% in 15 min. The dissolution profile of all the selected brands was within the standard limits and was acceptable.

Conclusions. Analytical method development is an integral part of the quality control measurements and evaluation of dissolution tests. Our previously developed HPLC method is essential for quality control of a large number of samples in short time intervals. Therefore, the method developed by our group is suitable for a routine quality control analysis of any pharmaceutical preparation containing two tested drugs with the suggested chromatographic method advantages for checking quality during dissolution studies of their dosage forms.

Author Biography


Assistant Professor, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine


Gupta KR, Wadodkar AR, Wadodkar SG. UV Spectrophotometric methods for estimation of Valsartan in bulk and tablet dosage form. Inter­national Journal of ChemTech Research. 2010;2:985-89.

Rao GS, Rao GV, Vardhan S, Ramachandran D. Development and validation of new UV-spectro­photometric assay method for valsartan in pure and in formulations. Journal of Chemical and Phar­ma­ceutical Research. 2013;5:229-32.

Ramachandran S, Mandal BK, Navalgund SG. Simultaneous spectrophotometric determination of valsartan and ezetimibe in pharmaceuticals. Tropical Journal of Pharmaceutical Research 2011;10:809-15.

DOI: https://doi.org/10.4314/tjpr.v10i6.15

Nikam MB, Dhamane H, Aligave A, Konda­war MS. Simultaneous estimation of valsartan, am­lodipine besylate and hydrochlorothiazide by first order derivative UV spectrophotometric method. Int J Pharm Technol. 2010;2:642-50.

Selvan PS, Gowda KV, Mandal U, Solomon WDS, Pal TK. Simultaneous determination of fixed dose combination of nebivolol and valsartan in human plasma by liquid chromatographic-tandem mass spectrometry and its application to pharmacokinetic study. Journal of Chromatography B. 2007;858:143-50.

DOI: https://doi.org/10.1016/j.jchromb.2007. 08.016

Sabi-mouka EMB, Agbokponto JE, Zhang R, Li Q, Ding L. Simultaneous determination of a fixe­ddose combination of lercanidipine and valsartan in human plasma by LC–MS-MS: Application to a phar­macokinetic study. Journal of chromatographic scien­ce. 2016;54:1553-59.

DOI: https://doi.org/10.1093/chromsci/bmw102

Koseki N, Kawashita H, Hara H, Niina M, Tanaka M, Kawai R, Nagae Y, Masuda N. Development and validation of a method for quantitative deter­mination of valsartan in human plasma by liquid chromatography-tandem mass spectrometry. Jour­nal of pharmaceutical and biomedical analysis. 2007;43:1769-74.

DOI: https://doi.org/10.1016/j.jpba.2006.12.030

Tian DF, Tian XL, Tian T, Wang ZY, Mo FK. Simultaneous determination of valsartan and hydrochlorothiazide in tablets by RP-HPLC. Indian journal of pharmaceutical sciences. 2008;70:372.

DOI: https://doi.org/10.4103/0250-474X.43006

Chitlange SS, Bagri K, Sakarkar DM. Stability Indicating RP-HPLC Method for Simultaneous Esti­mation of Valsartan and Amlodipine in Capsule Formulation. Asian Journal of Research in Chemistry. 2008;1:15-18.

Galande VR, Baheti KG, Indraksha S, Dehghan MH. Estimation of amlodipine besylate, valsartan and hydrochlorothiazide in bulk mixture and tablet by UV spectrophotometry. Indian journal of pharmaceutical sciences. 2011;74:18.

DOI: https://doi.org/10.4103/0250-474X.102538

Liu F, Zhang J, Xu Y, Gao S, Guo Q. Simultaneous determination of hydrochlorothiazide and valsartan in human plasma by liquid chromatography/tandem mass spectrometry. Analytical Letters. 2008;41:1348-65.

DOI: https://doi.org/10.1080/00032710802119186

Thanusha G, Jose C, Babu G, Basavaraj KPC, Panditi VR, Sharadha C. Validated RP-HPLC method for the quantitative estimation of valsartan in bulk and pharmaceutical dosage forms. International Journal of ChemTech Research. 2010;2:1194-98.

Kumar PVS, Sahu M, Prasad KD, Shekhar MC. Development and validation of analytical method for the estimation of valsartan in pure and tablet dosage form by RP-HPLC method. Int. J. Res. Pharm. Chem. 2011;1:945-49.

Vinzuda DU, Sailor GU, Sheth NR. RP-HPLC method for determination of valsartan in tablet dosage form. International Journal of ChemTech Research. 2010;2:1461-67.

Kendre MD, Banerjee SK. Precise and accu­rate RP-HPLC method development for quantification of valsartan in tablet dosage form. International Journal of Pharmaceutical Sciences and Drug Re­search. 2012;4:137-39.

Gonzalez L, Lopez JA, Alonso RM, Jimenez RM. Fast screening method for the determination of angiotensin II receptor antagonists in human plasma by high-performance liquid chromatography with fluorimetric detection. Journal of Chromatography A. 2002;949:49-60.

DOI: https://doi.org/10.1016/S0021-9673(01)01496-0

Lalitha G, Salomi P, Ravindra RK. Development of an analytical method and its validation for the analysis of atenolol in tablet dosage form by UV-Spectrophotometry. International Journal of Phar­macy and Pharmaceutical Sciences. 2013;5: 197–99.

Attia KA-SM, Nassar MW, Abolmagd E. Si­multaneous spectrophotometric determination of am­lodipine and atenolol in pharmaceutical prepara­tions using chemometric techniques. ACAIJ. 2016;16:205-10.

Lalitha KV, Kiranjyothi R, Padma B. UV Spectrophotometric method development and vali­dation for the determination of Atenolol and Losar­tan Potassium by Q-analysis. International Bul­letin of Drug Research. 2013;3:54-62.

Agarwal R, Gfadnis A. Kinetic spectro­photometric determination of atenolol in perchloric acid medium. International Journal of Pharmacy and Pharmaceutical Sciences. 2012;4:350-52.

Basavaiah K, Chandrashekar U, NagegowdaP. Titrimetric, spectrophotometric and kinetic methods for the assay of atenolol using bromate-bromide and methyl orange. Journal of the Serbian Chemical So­ciety. 2006;71:553-63.

DOI: https://doi.org/10.2298/JSC0605553B

Pai NR, Patil SS. Development and validation of liquid chromatographic method for atenolol and its related substance. Der Pharm. Sin. 2013;4:76-84.

Naikini P, Akula A, Ajitha A, Rao VUM. RP-HPLC method development and validation for the simultaneous estimation of amlodipine and atenolol in bulk and tablet dosage forms. International Journal of Pharmacy and Pharmaceutical Sciences. 2014;6:390-94.

Chaudhari V, Hussian S, Ubale M. A newer validated and stability indicating HPLC method for the estimation of Atenolol and Hydrochlorothiazide in bulk drug and dosage form. International Journal of Chemical Studies. 2013;1:93-101.

Belal F, Sharaf M, Aly F, Hefnawy M, Awady M. Stability-indicating HPLC Method for the Deter­mination of Atenolol in Pharmaceutical Preparations. J Chromat Separation Techniq. 2013;4:1-7.

Yilmaz B, Arslan S, Determination of atenolol in human urine by gas chromatography-mass spectrometry method. Journal of chromatographic science. 2011;49:365-69.

DOI: https://doi.org/10.1093/chromsci/49.5.365

Tengli AR, Gurupadayya BM. Method deve­lopment and validation of tablet dosage form con­taining losartan, atenolol and hydrochlorthiazide using internal standard by RP-HPLC. J Chromat Sepa­ration Techniq. 2013;4:1-5.

Gradman AH, Basile JN, Carter BL, Bakris GL. American Society of Hypertension Writing, G., Combination therapy in hypertension. Journal of the American Society of Hypertension. 2010;4:90-98.

DOI: https://doi.org/10.1016/j.jash.2010.03.001

Hanson R, Gray V. Handbook on Dissolution Testing. 3rd ed. Publisher: Dissolution Techno­logiesgies, USA, 2004. 199 р.

Guidance for industry: Waiver of in vivo bio­availability and bioequivalence studies for immediate-release solid oral dosage forms based on a Bio­phar­maceutics Classification System / U.S. Department of Health and Human Services, Food and Drug Administration (HHS-FDA). Center for Drug Evaluation and Research (CDER). 2017. URL: https://www.fda.gov/media/70963/download

DOI: http://academy.gmp-compliance.org/guidemgr/files/UCM070246.PDF.

Popy FA, Dewan I, Parvin MN, Islam SMA. Evaluation of in vitro equivalence for tablets con­taining the poorly water-soluble compound ator­vastatin. Dissol Technol. 2012;19(4):30-33.

DOI: https://doi.org/10.14227/DT190412P30

Costa P, Lobo JMS. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13:123–33.

DOI: https://doi.org/10.1016/S0928-0987(01)00095-1




How to Cite

Peleshok, K. Y. (2021). QUALITY CONTROL MEASUREMENT AND IN VITRO BIOEQUIVALENCE OF VALSARTAN AND ATENOLOL TABLETS MARKETED IN UKRAINE. International Journal of Medicine and Medical Research, 6(2), 52–58. https://doi.org/10.11603/ijmmr.2413-6077.2020.2.12013