Stability Indicating HPLC Method for Simultaneous Determination of Several Angiotensin-II-Receptor Antagonists in Their Dosage Forms

Abstract

A stability-indicating reversed-phase liquid chromatographic (RP-HPLC) method has been established for simultaneous determination of four angiotensin-II-receptor antagonists (Losartan potassium, Valsartan, Telmisartan and Irbesartan) in the presence of the degradation products generated in studies of forced decomposition. All drug substances were subjected to drastic condition of stress studies involving hydrolysis by acid and base, thermal decomposition by heat at 70°C, oxidation by hydrogen peroxide and photo degradation. Losartan potassium and Valsartan were degraded acidic conditions. Irbesartan was degraded basic conditions. Telmisartan showed good stability against all stress conditions. Successful separation of the drugs from the degradation products was achieved on ACE C18 column (250 mm×4.6 mm, 5 μm) with 65:35 % (v/v) potassium dihydrogen phosphate (0.025 M, pH 6.0): acetonitrile as a mobile phase at flow rate 1.5 ml/min with UV detection at 220 nm. The proposed method was validated in terms of linearity, accuracy, precision and limits of detection and quantitation. Statistical analysis proved the method enabled reproducible and selective quantification of these drugs as the bulk drug and in pharmaceutical dosage forms. Because the method effectively separates the drugs from their degradation products, it can be used as stability-indicating.

Stability‐indicating HPLC‐DAD Method for Simultaneous Determination of Atorvastatin, Irbesartan, and Amlodipine in Bulk and Pharmaceutical Preparations

“…Stress conditions involve acidic and basic hydrolysis, oxidation, exposure to UV light, and exposure to temperature (dry heat). However, from a literature survey it was evident that many stability‐indicating HPLC methods are designed for the determination of atorvastatin, irbesartan, and amlodipine, separately . Interestingly, one ultrahigh performance liquid chromatography (UPLC) method was reported on the combined determination of atorvastatin, amlodipine, and irbesartan with hydrochlorothiazide, but the authors worked with single dose of each compound and the method lacked the stability‐indicating nature…”

“…Irbesartan was found to be less stable to acid and alkaline hydrolysis (Figure ), resulting in 55% and 45% decomposition, respectively. It was also reported that irbesartan hydrolyzed by the breakage of the amide link in 1,3‐diazaspiro [4.4] non‐1‐en‐4‐one, which was identified as ((1‐(1‐((2 ( E ‐(1 H ‐tetrazol‐5‐yl) biphenyl‐4‐yl) methyl amino) pentylidene amino)cyclopentane carboxylic acid)) . Acidic hydrolysis results of amlodipine showed no change; therefore it can be concluded that it is stable in this condition.…”

“…It was also reported that irbesartan hydrolyzed by the breakage of the amide link in 1,3-diazaspiro [4.4] non-1-en-4-one, which was identified as ((1-(1-((2 (E-(1H-tetrazol-5yl) biphenyl-4-yl) methyl amino) pentylidene amino)cyclopentane carboxylic acid)). 13,15 Acidic hydrolysis results of amlodipine showed no change; therefore it can be concluded that it is stable in this condition. However, under basic conditions, amlodipine was found to be unstable ( Figure 5), and 63% decomposed.…”

“…However, from a literature survey it was evident that many stability-indicating HPLC methods are designed for the determination of atorvastatin, irbesartan, and amlodipine, separately. 3,[9][10][11][12][13] Interestingly, one ultrahigh performance liquid chromatography (UPLC) method was reported on the combined determination of atorvastatin, amlodipine, and irbesartan with hydrochlorothiazide, but the authors worked with single dose of each compound and the method lacked the stability-indicating nature. 5 To the best of our knowledge, there is no reported analytical method that estimates all above drugs simultaneously.…”

Investigation of the Physical, Chemical and Microbiological Stability of Losartan Potassium 5 mg/mL Extemporaneous Oral Liquid Suspension

“…Losartan potassium (Losartan) extemporaneous oral suspensions were prepared by the method used in Children’s Health Ireland at Crumlin, Ireland (method A) and as per published monographs [ 10 , 11 ] (method B), without and with addition of water, respectively. Losartan (as losartan potassium) concentration was measured over 28 days, using UV spectroscopy and a stability indicating HPLC method [ 15 , 16 ]. Suspensions were monitored for changes in pH, colour, odour and re-dispersibility.…”