ANALYTICAL STUDY AND IMPURITY PROFILING OF FIXED DOSES COMBINATION OF AMLODIPINE, HYDROCHLOROTHIAZIDE AND OLMESARTAN BY RP-HPLC AND UPLC
Abstract
A specific and sensitive reverse phase high pressure liquide chromatography (RP-HPLC) and ultra-performance liquide chromatography (UPLC) method for the determination of related substances for fixed-dose combination formulation of Amlodipine Besylate, Hydrochlorothiazide and Olmesartan Medoxomil was developed and validated. By using the gradient RP-HPLC method, a total of 25 known and unknown impurities related to Amlodipine Besylate, Hydrochlorothiazide and Olmesartan Medoxomil in combination formulation were separated and quantified in the linearity range of (0.2 to 3.0 μg/mL) for Amlodipine Besylate, (0.5 to 7.5 μg/mL) for Hydrochlorothiazide and (0.8 to 12.0 μg/mL) for Olmesartan Medoxomil with good squared correlation (>0.99). The recovery study was established from LOQ (0.05%) to 150% of the specification limit. A precision study was performed by spiking each known impurities at the specification level. In this study, two separate analytical methods RP-HPLC and UPLC have been developed, validated, and compare for the simultaneous quantification of Amlodipine Besylate, Hydrochlorothiazide, and Olmesartan Medoxomil tablets with their impurities. In these methods total of 28 peaks were separated in 70 minutes run time by HPLC method while in 45 minutes by UPLC method. Both the methods are developed with high selectivity, sensitivity, and robustness to separate 28 peaks in a single method. The proposed methods have a high degree of sensitivity and will provide fast and cost-effective quantitative control of Pharmaceutical formulations.
Keywords:
Amlodipine Besylate, Hydrochlorothiazide HCl, Olmesartan Medoxomil, High-pressure chromatographic system (HPLC), UPLCDOI
https://doi.org/10.25004/IJPSDR.2022.140103References
Gao P, Mei K, Li H, Dai Q, Guo X, Zhang D, Jin Z, You H, Ding H, Lü K, Zhou S, Peng X, Xu H, Yin P, Yu L, Pi L, Hua Q, Yang M, Yu X. Clinical Efficacy and Safety of Combination Therapy with Amlodipine and Olmesartan or an Olmesartan/Hydrochlorothiazide Compound for Hypertension: A Prospective, Open-Label, and Multicenter Clinical Trial in China. Curr. Ther. Res. 2019;90:99-105. Available from: doi. org/10.1016/j.curtheres.2015.09.001
Guerrero GC, Rubio GAF. Combination therapy in the treatment of hypertension. Drugs in Context. 2018;7:212531. Available from: doi.org/10.7573/dic.212531
Gradman AH, Basile JN, Carter BL, Bakris GL. Combination Therapy in Hypertension. The J. of Clinical Hypertension. 2011;13:146-154. Available from: doi.org/10.1111/j.1751-7176.2010.00397.x
Mazza A, Lenti S, Schiavon L, Sacco AP, Dell’Avvocata F, Rigatelli G, Ramazzina E. Fixed-Dose Triple Combination of Antihypertensive Drugs Improves Blood Pressure Control: From Clinical Trials to Clinical Practice. Adv. Ther. 2017;34(4):975–985. Available from: doi.org/10.1007/s12325-017-0511-1
Burges RA, Michael GD, Amlodipine. Cardiovas. Drug Reviews. 1990;8(I):25–44. Available from: doi.org/10.1111/j.1527-3466.1990. tb00427.x
Tatu AL, Ciobotaru OM, Magdalena M, Buzia OD, Elisei AM, Mardare N, Diaconu C., Robu S,Nwabudike LC. Hydrochlorothiazide: Chemical Structure, Therapeutic, Phototoxic and Carcinogenetic Effects in Dermatology. Rev. Chim. 2018;69(8):2110-2124. Available from: doi.org/10.37358/RC.18.8.6484
Kellici T, Ntountaniotis D, Vrontaki E, Liapakis G, Moutevelis MP, Kokotos G, Hadjikakou S, Tzakos AG, Afantitis A, Melagraki G, Bryant S, Langer T, Marzo DV, Mavromoustakos T. Rational drug design paradigms: the odyssey for designing better drugs. Comb. Chem. High Throughput Screening. 2015;18(3):238-256. Available from: doi.org/10.2174/1386207318666150305125638
Pai NR, Sawant SS. Development and Validation of New RP-HPLC Method for Determining Impurit y Profiling in Olmesartan Medoxomil Drug as Well as in Tablet Dosage Form. Der Pharma Chemica. 2013;5(4):274–281. Available from: https://rjptonline. org/AbstractView.aspx?PID=2013-6-11-12
Sharma RN, Pancholi SS. RP-HPLC-DAD Method for Determination of Olmesartan Medoxomil in Bulk and Tablets Exposed to Forced Conditions. A cta pharm. 2010; 6 0(1):13–24. A vailable f rom: doi. org/10.2478/v10007-010-0010-2
Shaalan R A , Belal TS, El Yazbi FA , Elonsy SM. Validated stabilit y-indicating HPLC-DAD method of analysis for the antihypertensive triple mixture of amlodipine besylate, valsartan and hydrochlorothiazide in their tablets. Arabian J. Chem. 2013;10(1):S1381-S1394. Available from: doi.org/10.1016/j. arabjc.2013.04.012
Mali AD, More UB. Development and Validation of RP-HPLC Method for Simultaneous Estimation of impurities from Olmesartan Medoxomil and Hydrochlorothiazide Tablet. Int. J. Pharm. Pharm. Sci. 2016;8(5):45–48. Available from: https://innovareacademics. in/journals/index.php/ijpps/article/view/10890
Prasad VD, Rangareddy V, Aparna P. Method Development Work on Separation and Simultaneous Determination of Specified and Unspecified Impurities of Amlodipine Besilate, Hydrochlorothiazide and Olmesartan Medoxomil Film-Coated Tablets. Int. J. Pharm. Sci. Helthc. 2015;5(5):1–9. Available from: http://www.rspublication. com/ijphc/2015/oct15/oct15.htm
Desai PR, Mehta PJ, Chokshi AB. Stability indicating RP HPLC Method Development and Validation for Simultaneous Quantification of 15 Organic Impurities of Olmesartan Medoxomil, Amlodipine and Hydrochlorothiazide in Combined Dosage Form. Chromatographia. 2019;82(5):819–833. Available from: doi. org/10.1007/s10337-019-03718-9
Panchal JG, Patel RV, Mistry BR, Menon SK. Development and Validation of Reversed-Phase LC Method Forsimultaneous Determination Telmisartan, Amlodipine and their degradation products in Fixed Dose Combination Tablets. Eurasian J. Anal. Chem. 2012;7(1):28–42. Available from: https://www.eurasianjournals. com/abstract.php?id=129
Shitole S, Gurjar M, Shah M, Pimple S, Pawar N, Pawar A. Development and validation of a stability indicating rp-hplc method for simultaneous estimation of related substances of s (-) amlodipine and telmisartan in fixed dose combination tablet dosage form. Int. J. Univers. Pharm. Bio Sci. 2014;3(4):194-206. Available from: http:// ijupbs.com/Current_Issue.aspx?key=Volume3%20Issue4%202014
Suresh RS, Manavalan R, Valliappan K. Developing and optimizing a validated RP-HPLC method for the analysis of amlodipine and ezetimibe with atorvastatin in pharmaceutical dosage forms applying response surface methodology. International Journal of Pharmacy and Pharmaceutical Sciences. 2012;4(3):550-558. Available from: https://innovareacademics.in/journal/ijpps/ Vol4Issue3.htm
Rao CK, Kumar KK, Maddala V, Shrinivasulu P, Madhusudan G, Mukkanti K, Srinivas KSV. Development and Validation of Stability Indicating LC Method for Olmesartan Medoxomil. Am. J. Anal. Chem. 2012;03(2):153-160. Available from: doi.org/10.4236/ ajac.2012.32022
Hafez HM, Elshanawany AA, Abdelaziz LM, Mohram MS. Development of a Stability-Indicating HPLC Method for Simultaneous Determination of Amlodipine Besylate and Atorvastatin Calcium in Bulk and Pharmaceutical Dosage Form. Pharm. Anal. Acta. 2014;5(9):316. Available from: doi.org/10.4172/2153-2435.1000316
Reddy MRM, Kumar AP, Reddy VK, Haque SW. Stability-indicating HPLC method for simultaneous estimation of low level impurities of Telmisartan and hydrochlorothiazide in tablet dosage forms. Int. J. Pharm. Pharm. Sci. 2012;4(1):497–504. Available from: https:// innovareacademics.in/journal/ijpps/Vol4Issue1.htm
Nalwade S, Vangala RR, Rao DD, Rao IK. Rapid Simultaneous Determinat ion of Telmisar t an, Amlodipine Besylate and Hydrochlorothiazide in a Combined Poly Pill Dosage Form by Stability-Indicating Ultra Performance Liquid Chromatography. Sci. Pharm. 2011;79(1):69-84. Available from: doi.org/10.3797/ scipharm.1006-10
Kumar SA, Debnath M, Rao JVLNS, Sankar DG. A New and Rapid Analytical Method Development & Validation for Simultaneous Estimation of Hydrochlorothiazide, Amlodipine & Olmesartan in Tablet Dosage Form by Using RP-HPLC. J. Chem. Pharm. Res. 2014;6(5):1208–1213. Available from: https://www.jocpr.com/ archive/jocpr-volume-6-issue-5-year-2014.html
Sinojiya RS, Khasia V, Patel BJ, Dangi AA. Development and Validation of Rp-HPLC Method for the Simultaneous Determination of Telmisartan, Amlodipine Besylate & Hydrochlorothiazide in a Tablet Dosage Form. J. Pharmacy Res. 2012;5(8):4154–4157.
Tengli AR, Shivakumar G, Gurupadayya BM. UPLCMS Method Development and Validation of Amlodipine, Hydrochlorthiazide and Losartan in Combined Tablet Dosage Form. Am. J. Anal. Chem. 2015;6:228-238. Available from: doi.org/10.4236/ajac.2015.63021
Napa DR, Sockalingam A, Kunapareddy AB, Sunkara NB, Chusena NB. Validated Stability Indicating Gradient RP-HPLC Method for the Estimation of Antihypertensive Drugs in Bulk and Pharmaceutical Dosage Forms. Int. Curr. Pharm. J. 2012;1(11):336–341. Available from: doi.org/10.3329/icpj.v1i11.12058
Panchumarthy R, Devala RG, Sulathana MDS, Supriya K, Mounika G, Naveena P. Rapid and economical quantitative determination of several antihypertensive agents in presence of hydrochlorothiazide by isocratic reversed-phase high-performance liquid chromatography in their pharmaceutical preparations. Asian J. Pharm. Clin. Res. 2017;10(12):155-159. Available f rom: https://innovareacademics.in/journals/index.php/ajpcr/article/ view/18714
JainPS, Patel MK, Gorle AP, ChaudhariAJ, Surana SJ. Stability- Indicating Method for Simultaneous Estimation of Olmesartan Medoxomile, Amlodipine Besylate and Hydrochlorothiazide by RP-HPLC in Tablet Dosage Form. J. Chromatogr. Sci. 2012; 50(8):680–687. Available from: doi.org/10.1093/chromsci/bms067
Published
Abstract Display: 682 
PDF Downloads: 1010 
