A Validated Stability Indicating RP-HPLC Method Development and Validation for Simultaneous Estimation of Aliskiren Hemifumarate and Amlodipine Besylate in Pharmaceutical Dosage Form

The present study describes the stability indicating RP-HPLC method for simultaneous estimation of aliskiren hemifumarate and amlodipine besylate in pharmaceutical dosage forms. The proposed RP-HPLC method was developed by using waters 2695 separation module equipped with PDA detector and chromatographic separation was carried on C-8 Inertsil ODS (150 × 4.6？mm, 5？μ) column at a flow rate of 1？mL/min and the run time is 10？min. The mobile phase consisted of phosphate buffer and acetonitrile in the ratio of 40？:？60%？v/v and pH was adjusted to 3 with orthophosphoric acid and eluents were scanned using PDA detector at 237？nm. The retention time of aliskiren and amlodipine was found to be 3.98 and 5.14？min, respectively. A linearity response was observed in the concentration range of 30–225？μg/mL for aliskiren and 2–15？μg/mL for amlodipine, respectively. Limit of detection and limit of quantification for aliskiren are 0.161？μg/mL and 0.489？μg/mL and for amlodipine are 0.133？μg/mL and 0.404？μg/mL, respectively. The stability indicating method was developed by subjecting the drugs to stress conditions such as acid and base hydrolysis, oxidation, and photo- and thermal degradation and the degraded products formed were resolved successfully from the samples. 1. Introduction Aliskiren is a novel antihypertensive agent and is the first orally active rennin inhibitor indicated for the treatment of hypertension [1–3]. Chemically, aliskiren is (2S, 4S, 5S, 7S)-N-(2-carbamoyl-2-methylpropyl)-5-amino-4-hydroxy-2,7-diisopropyl-8-[4-methoxy-3-(3-methoxypropoxy) phenyl]-octanamide [4] (Figure 1(a)). Renin is secreted by the kidney, which cleaves the angiotensinogen to form angiotensin I and is then converted into angiotensin II by angiotensinogen converting enzyme. Aliskiren inhibits the catalytic activity of rennin system and inhibits the generation of angiotensin I and angiotensin II [5–7]. Figure 1: (a) Chemical structure of aliskiren. (b) Chemical structure of amlodipine. Amlodipine is a member of 1, 4-dihydropyridine class of calcium antagonist approved for the treatment of heart diseases like hypertension and angina pectoris. It is a long acting calcium channel blocker that inhibits the influx of calcium ions into the vascular smooth muscle and cardiac muscle [8, 9]. Chemically amlodipine is 3-ethyl-5-methyl 2-[(2-aminoethoxy) methyl]-4-(2-chlorophenyl)-1,4-dihydropyridine-6-methyl-3,5-dicarboxylate [10] (Figure 1(b)). Through literature survey reveals that there are few analytical methods such as RP-HPLC [11, 12] and UV methods [13, 14] are reported for