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Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

Development and Validation of an Analytical RP-HPLC Method for Simultaneous Estimation of Losartan and its Active Metabolite (EXP-3174) in Isolated Perfused Rat Liver

Author(s): Mahsa Toolabi, Reyhaneh Ramezankhani, Nadereh Rahbar, Maryam Dibaei, Alireza Foroumadi, Hoda Lavasani, Vida Kazemi and Mohammadreza Rouini*

Volume 19, Issue 10, 2023

Published on: 06 December, 2023

Page: [786 - 793] Pages: 8

DOI: 10.2174/0115734129272952231103080114

Price: $65

Abstract

Background: The liver perfusion method is frequently used in drug pharmacokinetic studies and the various effects of drugs on liver tissue. The aim of this study was to establish and validate an analytical method using high-performance liquid chromatography to determine the simultaneous concentration of losartan and its active metabolite, EXP-3174, in an isolated perfused rat liver study.

Method: An HPLC system with isocratic mode was used. Various chromatographic parameters were adjusted to develop and validate a method for determination of losartan and its active metabolite in liver perfusion media.

Results: In this study, losartan and its active metabolite, EXP-3174, were separated using a C18 stationary phase, a mobile phase consisting of acetonitrile: phosphate buffer at a flow rate of 1 mL.min-1, and UV detection at 254 nm. Retention times for losartan and the metabolite were 10 and 16 minutes, respectively. Linearity from 25-250 ng.ml-1 was validated with acceptable accuracy and precision. The LOD and LOQ for losartan were 7.0 and 21.1 ng.ml-1, respectively. The LOD and LOQ for metabolite were 7.4 and 22.4 ng.ml-1, respectively. ChromGate® software was used to acquire and process the data.

Conclusions: The optimized and validated technique was effectively used to analyze losartan and its active metabolite in isolated perfused rat liver.

Graphical Abstract

[1]
Ganguly, P; Almiro, A; Dawalibi, A; Al Mahayni, T; Mohammad, K.S. Central Control of Sympathetic and Renin Angiotensin System in the Development of Hypertension. In:The Renin Angiotensin System in Cardiovascular Disease. Cham:; Springer International Publishing., 2023, pp. 173-185.
[http://dx.doi.org/10.1007/978-3-031-14952-8_11]
[2]
Paz Ocaranza, M.; Riquelme, J.A.; García, L.; Jalil, J.E.; Chiong, M.; Santos, R.A.S.; Lavandero, S. Counter-regulatory renin–angiotensin system in cardiovascular disease. Nat. Rev. Cardiol., 2020, 17(2), 116-129.
[http://dx.doi.org/10.1038/s41569-019-0244-8] [PMID: 31427727]
[3]
Miller, A.J.; Arnold, A.C. The renin–angiotensin system in cardiovascular autonomic control: Recent developments and clinical implications. Clin. Auton. Res., 2019, 29(2), 231-243.
[http://dx.doi.org/10.1007/s10286-018-0572-5] [PMID: 30413906]
[4]
Abdel Ghafar, M.T. An overview of the classical and tissue-derived renin-angiotensin-aldosterone system and its genetic polymorphisms in essential hypertension. Steroids, 2020, 163, 108701.
[http://dx.doi.org/10.1016/j.steroids.2020.108701] [PMID: 32717198]
[5]
Amini, H.; Ahmadiani, A.; Moazenzadeh, M. Pharmacokinetics of losartan and its active metabolite EXP3174 in healthy iranian subjects. Clin. Drug Investig., 2004, 24(10), 619-623.
[http://dx.doi.org/10.2165/00044011-200424100-00008] [PMID: 17523724]
[6]
Shah, P.A.; Sharma, P.; Shah, J.V.; Sanyal, M.; Shrivastav, P.S. Simultaneous analysis of losartan, its active metabolite, and hydrochlorothiazide in human plasma by a UPLC-MS/MS method. Turk. J. Chem., 2015, 39(4), 714-733.
[http://dx.doi.org/10.3906/kim-1502-4]
[7]
Tamimi, J.J.I.; Salem, I.I.; Mahmood Alam, S.; Zaman, Q.; Dham, R. Comparative pharmacokinetics of two tablet formulations of Losartan: Bioequivalence assessment. Biopharm. Drug Dispos., 2005, 26(5), 205-210.
[http://dx.doi.org/10.1002/bdd.448] [PMID: 15906418]
[8]
Wani, T.U.; Mir, K.B.; Raina, A.; Dar, A.A.; Jan, I.; Khan, N.A.; Wani, T.A.; Sofi, J.A.; Hassan, G.I.; Almoallim, H.S.; Alharbi, S.A.; Ansari, M.J.; Alfarraj, S.; Tarique, M.; Dar, S.A. Simultaneous quantification of losartan potassium and its active metabolite, EXP3174, in rabbit plasma by validated HPLC–PDA. Biomed. Chromatogr., 2023, 37(8), e5645.
[http://dx.doi.org/10.1002/bmc.5645] [PMID: 37052130]
[9]
Abd El-Hay, S.S.; Elhenawee, M.; Maged, K.; Ibrahim, A.E. Cost-effective, green HPLC determination of losartan, valsartan and their nitrosodiethylamine impurity: application to pharmaceutical dosage forms. R. Soc. Open Sci., 2022, 9(6), 220250.
[http://dx.doi.org/10.1098/rsos.220250] [PMID: 35706671]
[10]
Vivekanandan, N.; Santhi, N.; Rajendran, S.S.; Kumar, S.S. Development and validation of rp-hplc method for the simultaneous estimation of losartan potassium and hydrochlorthiazide in bulk and tablet dosage form. Int. J. Chem. Pharmaceut. Anal., 2022, 10(1)
[11]
Yeung, P.K.F.; Pollak, P.T.; Jamieson, A.; Smith, G.J.; Fice, D. Determination of plasma concentrations of losartan in patients by HPLC using solid phase extraction and UV detection. Int. J. Pharm., 2000, 204(1-2), 17-22.
[http://dx.doi.org/10.1016/S0378-5173(00)00453-1] [PMID: 11011981]
[12]
Oh, K.S.; Park, S.J.; Shinde, D.D.; Shin, J.G.; Kim, D.H. High-sensitivity liquid chromatography–tandem mass spectrometry for the simultaneous determination of five drugs and their cytochrome P450-specific probe metabolites in human plasma. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2012, 895-896, 56-64.
[http://dx.doi.org/10.1016/j.jchromb.2012.03.014] [PMID: 22483397]
[13]
Wadie, M.A.; Kishk, S.M.; Darwish, K.M.; Mostafa, S.M.; Elgawish, M.S. Simultaneous determination of losartan and rosuvastatin in rat plasma using liquid chromatography–tandem mass spectrometric technique for application into pharmacokinetic and drug–drug interaction studies. Chromatographia, 2020, 83(12), 1477-1494.
[http://dx.doi.org/10.1007/s10337-020-03967-z]
[14]
Hong, Y.; He, G.; Lu, J.; Xu, Y. Profiling detection and validation of six sartan substances in human urine by LC-MS/MS. J. Anal. Chem., 2023, 78(8), 1041-1054.
[http://dx.doi.org/10.1134/S1061934823080063]
[15]
Sri-in, J; Thanakosai, W. Liquid chromatography tandem mass spectrometry method for simultaneous determination of losartan and its active metabolite in human plasma. Pharmaceut. Sci. Asia., 2018, 45(4), 252-262.
[http://dx.doi.org/10.29090/psa.2018.04.018.0012]
[16]
Soldner, A.; Spahn-Langguth, H.; Mutschler, E. HPLC assays to simultaneously determine the angiotensin-AT1 antagonist losartan as well as its main and active metabolite EXP 3174 in biological material of humans and rats. J. Pharm. Biomed. Anal., 1998, 16(5), 863-873.
[http://dx.doi.org/10.1016/S0731-7085(97)00128-3] [PMID: 9535198]
[17]
Farthing, D.; Sica, D.; Fakhry, I.; Pedro, A.; Gehr, T.W.B. Simple high-performance liquid chromatographic method for determination of losartan and E-3174 metabolite in human plasma, urine and dialysate. J. Chromatogr., Biomed. Appl., 1997, 704(1-2), 374-378.
[http://dx.doi.org/10.1016/S0378-4347(97)00489-1] [PMID: 9518174]
[18]
Gores, G.J.; Kost, L.J.; Larusso, N.F. The isolated perfused rat liver: Conceptual and practical considerations. Hepatology, 1986, 6(3), 511-517.
[http://dx.doi.org/10.1002/hep.1840060331] [PMID: 3519420]
[19]
Liu, Y; Weber, SJ; Onua, ET.; Liu, Y; Weber, SJ; Onua, ET. Hepatic clearance and drug metabolism using isolated perfused rat liver. Curr. Protoc. Pharmacol., 2004. Oct 1;Chapter 7:Unit 7.9;
[http://dx.doi.org/10.1002/0471141755.ph0709s26]
[20]
Pirali-Hamedani, M.; Aliabadi, A.; Shekarchi, M.; Amini, M.; Rouini, M.R.; Shafiee, A.; Foroumadi, A. A convenient method for the preparation of losartan active metabolite (EXP-3174). Asian J. Chem., 2009, 21(6), 4909.
[21]
Ritter, M.A.; Furtek, C.I.; Lo, M.W. An improved method for the simultaneous determination of losartan and its major metabolite, EXP3174, in human plasma and urine by high-performance liquid chromatography with fluorescence detection. J. Pharm. Biomed. Anal., 1997, 15(7), 1021-1029.
[http://dx.doi.org/10.1016/S0731-7085(96)01948-6] [PMID: 9160270]
[22]
Takayama, F.; Saito, K.; Yoshinaga, T.; Morita, M.; Hata, S.; Esumi, Y.; Jin, Y.; Okamura, Y. Metabolic fate of losartan, a new angiotensin II receptor antagonist (1): absorption, distribution, metabolism and excretion after single administration in rats. Drug Metab. Pharmacokinet., 1995, 10(2), 223-243.
[http://dx.doi.org/10.2133/dmpk.10.223]
[23]
Christ, D.D. 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(5), 515-520.
[http://dx.doi.org/10.1002/j.1552-4604.1995.tb04097.x] [PMID: 7657853]
[24]
Taki, Y.; Sakane, T.; Nadai, T.; Sezaki, H.; Amidon, G.L.; Langguth, P.; Yamashita, S. First-pass metabolism of peptide drugs in rat perfused liver. J. Pharm. Pharmacol., 2011, 50(9), 1013-1018.
[http://dx.doi.org/10.1111/j.2042-7158.1998.tb06916.x] [PMID: 9811162]
[25]
Yasar, U.; Forslund-Bergengren, C.; Tybring, G.; Dorado, P.; Llerena, A.; Sjöqvist, F.; Eliasson, E.; Dahl, M.L. Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9 genotype. Clin. Pharmacol. Ther., 2002, 71(1), 89-98.
[http://dx.doi.org/10.1067/mcp.2002.121216] [PMID: 11823761]
[26]
Cheung, K.; Hickman, P.E.; Potter, J.M.; Walker, N.I.; Jericho, M.; Haslam, R.; Roberts, M.S. An optimized model for rat liver perfusion studies. J. Surg. Res., 1996, 66(1), 81-89.
[http://dx.doi.org/10.1006/jsre.1996.0376] [PMID: 8954836]
[27]
Mehvar, R.; Chimalakonda, A.P. Hepatic disposition of cyclosporine A in isolated perfused rat livers. J. Pharm. Pharm. Sci., 2004, 7(1), 47-54.
[PMID: 15144734]
[28]
Bessems, M.; ’t Hart, N.A.; Tolba, R.; Doorschodt, B.M.; Leuvenink, H.G.D.; Ploeg, R.J.; Minor, T.; van Gulik, T.M. The isolated perfused rat liver: Standardization of a time-honoured model. Lab. Anim., 2006, 40(3), 236-246.
[http://dx.doi.org/10.1258/002367706777611460] [PMID: 16803641]

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