ISSN

0974-4150 (Online)
0974-4169 (Print)


Author(s): Alka Singh, Neeraj Upmanyu

Email(s): singhalka7160@gmail.com

DOI: 10.52711/0974-4150.2021.00047   

Address: Alka Singh, Neeraj Upmanyu
School of Pharmacy and Research, People’s University, Bhanpur, Bhopal (M.P.) India.
*Corresponding Author

Published In:   Volume - 14,      Issue - 4,     Year - 2021


ABSTRACT:
Background: The combination therapy of Losartan and active metabolite has proven to be beneficial as compare to either drug monotherapy. Losartan is a highly selective, orally active, non-peptide angiotensin II receptor antagonist indicated for the treatment of hypertension, which is one of the most important causes of mortality and morbidity in the modern world. It has a more potent active carboxylic acid metabolite EXP-3174 (2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol yl)phenyl]phenyl]methyl]imidazole-4-carboxylic acid). Losartan and its active carboxylic acid metabolite EXP-3174 block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by type ATI receptor blockage. Following oral administration, losartan is rapidly absorbed, reaching maximum concentrations 1–2 h post-dose. Result: The selected analytes were effectively separated on thermo ß-basic C18 (100×4.6 mm, 5 µm) column using mobile phase consisting of 20mM monobasic potassium phosphate and 0.2% TEA with acetonitrile and iso-propyl alcohol in gradient mode. The eluent was monitored at 228nm at 1.0 ml min-1 flow rate. The total run time was less than 12 min. Conclusion: The active carboxylic acid metabolite E-3174 is about ten times more potent than losartan. In healthy volunteers, the concentrations of the active carboxylic acid metabolite EXP-3174 were found to be more closely parallel angiotensin II antagonism than those of the parent compound. Thus, the angiotensin II blocking activity of losartan is predominantly based on its major active carboxylic acid metabolite EXP-3174. Given this as background and to our best knowledge, there is no HPLC-UV method available or published simultaneous estimation of losartan with its active metabolite.


Cite this article:
Alka Singh, Neeraj Upmanyu. Development and Validation of Analytical HPLC-UV Method for simultaneous estimation of Losartan and its active Metabolite EXP-3174. Asian Journal of Research in Chemistry. 2021; 14(4):275-1. doi: 10.52711/0974-4150.2021.00047

Cite(Electronic):
Alka Singh, Neeraj Upmanyu. Development and Validation of Analytical HPLC-UV Method for simultaneous estimation of Losartan and its active Metabolite EXP-3174. Asian Journal of Research in Chemistry. 2021; 14(4):275-1. doi: 10.52711/0974-4150.2021.00047   Available on: https://ajrconline.org/AbstractView.aspx?PID=2021-14-4-8


REFERENCES:
1.    Ezzati M, Vander Hoorn S, Lawes CM, et al. Rethinking the “diseases of affluence” paradigm: global patterns of nutritional risks in relation to economic development. PLoS Med 2005; 2: 133.
2.    Sica D. Rationale for fixed-dose combinations in the treatment of hypertension. Drugs 2002; 62: 443-462.
3.    Murray CJL, Lopez AD, editors (1996) The global burden of disease: A comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020. Cambridge (Massachusetts): Harvard School of Public Health. 990 p.
4.    Reddy KS, Yusuf S (1998) Emerging epidemic of cardiovascular disease in developing countries. Circulation 97: 596–601.
5.    Yusuf S, Reddy S, Ounpuu S, Anand S (2001) Global burden of cardiovascular diseases: Part I: General considerations, the epidemiological transition, risk factors, and impact of urbanization. Circulation 104: 2746– 2753.
6.    Bulatao RA (1993) Mortality by cause, 1970 to 2015. In: Gribble JN, Preston SH, editors. The epidemiological transition: Policy and planning implications for developing countries. Washington (D.C.): National Academy Press. pp. 42–68.
7.    Stearns RA, Chakravarty PK, Chen R, Chiu S. Biotransformation of losartan to its active carboxylic acid metabolite in human liver microsomes. Role of cytochrome P4502C and 3A subfamily members. Drug Metab Dispos. 1995; 23: 207-215.
8.    Obach RS. Pharmacologically active drug metabolites: impact on drug discoveryand pharmacotherapy. Pharmacol Rev. 2013; 65: 578-640.
9.    Lo M-W, Goldberg MR, McCrea JB, Lu H, Furtek CI, Bjornsson TD. Pharmacokinetics of losartan, an angiotensin II receptor antagonist, and its active metabolite EXP3174 in humans. Clin Pharmacol Ther. 1995; 58:641-649.
10.    Christ DD. Human plasma protein binding of the angiotensin II receptor antagonist losartan potassium (DuP 753/MK 954) and its pharmacologically active metabolite EXP3174. J Clin Pharmacol. 1995; 35: 515-520.
11.    Marciniak T. Clinical Review, Supplemental NDA Submission, NDA 20e386, Cozaar Tablets. Silver Spring, MD: Division of Cardiorenal Drug Products. U.S. Food and Drug Administration. Merck and Co; 2002.
12.    Gardiner P, Paine SW. The impact of hepatic uptake on the pharmacokinetics of organic anions. Drug Metab Dispos. 2011; 39: 1930-1938.

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