Stability Indicating RP-HPLC Method for Simultaneous Determination of Atorvastatin and Amlodipine from Their Combination Drug Products

Abstract

Atorvastatin 1) is a synthetic lipid lowering agent which inhibits HMG-CoA reductase and amlodipine 2) is a calcium antagonist drug effective in hypertension and angina pectoris. The combination drug product of atorvastatin (ATV) and amlodipine (AML) has recently been introduced in the market; co-administration of AML with ATV demonstrated statistically significant dose-related reductions in systolic blood pressure (SBP), diastolic blood pressure (DBP) and LDL-C in patients with co-morbid hypertension and dyslipidemia. 3)Chemically ATV is [R-(R*,R*)]-2-(4-fluorophenyl)-b, dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino) carbonyl]-1H-pyrrole-1-heptanoic acid, calcium salt (2 : 1) trihydrate 4) and AML is 2-[(2-Aminoethoxy)-methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester. 5)Stability testing forms an important part of the process of drug product development. The purpose of stability testing is to provide evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity, and light, and enables recommendation of storage conditions, retest periods, and shelf lives to be established. The two main aspects of drug product that play an important role in shelf life determination are assay of active drug, and degradation products generated, during the stability study. The assay of drug product in stability test sample needs to be determined using stability indicating method, as recommended by the International Conference on Harmonization (ICH) guidelines 6) and USP-26. 7) Although stability indicating methods have been reported for assay of various drugs in drug products, most of them describe assay procedures for drug products containing only one active drug substance. Only few stability indicating methods are reported for assay of combination drug products containing two or more active drug substances. The objective of this work was to develop a simple, precise and rapid analytical LC procedure, which would serve as stability indicating assay method for combination drug product of ATV and AML.Both methods have been reported for simultaneous determination of ATV and AML, but these methods lack stability indicating nature. None of the reported analytical procedures describe a stability indicating method for simultaneous determination of ATV and AML in presence of their degradation products. This manuscript describes the development and validation of a stability indicating isocratic reversed-phase HPLC method for simultaneous determination of ATV and AML in presence of their degradation products as per ICH guidelines. The study describes development and subsequent validation of a stability indicating reverse-phase HPLC method for the simultaneous estimation of atorvastatin (ATV), and amlodipine (AML) from their combination drug product. The proposed RP-HPLC method utilizes a Lichrospher ® 100 C 18 , 5 m mm, 250 mm؋4.0 mm i.d. column, at ambient temperature, optimum ...

A Review of Current Trends and Advances in Analytical Methods for Determination of Statins: Chromatography and Capillary Electrophoresis

“…There are a number of methods describing simultaneous determination of simvastatin and ezetimibe from their combination drug products [22][23][24][25]. Stability indicating studies on combined pharmaceutical products of simvastatin and ezetimibe have also been published [24,25].…”

“…Stability indicating studies on combined pharmaceutical products of simvastatin and ezetimibe have also been published [24,25]. Different approaches to forced degradation study, chromatographic conditions and determination of degradation products were performed.…”

New Kinetic Spectrophotometric Method for Determination of Atorvastatin in Pure and Pharmaceutical Dosage Forms

“…Atorvastatin calcium {[R-(R, R*)]-2-(4-flurophenyl)-β,δ-dihydroxy-5(1-methylethyl)-3-phenyl-4-[phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, calcium salt (2:1) trihydrate} is the most commonly occurring drug in commercially available pharmaceutical formulations used for the clinical treatment of hypercholesterolemia [1]. Several methods have been described for the quantitative determination of atorvastatin by high-performance liquid chromatography (HPLC) in different pharmaceutical preparations, either alone [2][3][4][5][6][7] or with other active ingredients [8][9][10][11][12][13][14][15][16]. HPTLC [17], electrochemical [18,19], capillary electrophoresis [20] and spectrofluorimetric [21] methods have been developed for the analysis of atorvastatin from its individual and combined formulations with other active ingredients in pharmaceutical preparations and plasma.…”

Development and Validation of Chiral HPLC Method for Identification and Quantification of (R)-Enantiomer in Ezetimibe

“…This reduces the overall delivery of cholesterol to the liver, there by promoting the synthesis of LDL receptors and the subsequent reduction in serum LDL-C [6,7]. Few HPLC methods for the determination of Ezetimibe and its pharmaceutical dosage forms were reported in literatures [8][9][10]. The (R)-enantiomer is an undesired enantiomer, which can be present as a chiral impurity without any pharmacological and toxicological reports by now.…”