Novel Stability-Indicating UHPLC Method Development and Validation for the Quantification of Perindopril, Amlodipine and
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ORIGINAL
Novel Stability‑Indicating UHPLC Method Development and Validation for the Quantification of Perindopril, Amlodipine and Their Impurities in Pharmaceutical Formulations: Application of QbD Approach T. S. S. Jagan Mohan1,2 · Hitesh A. Jogia3 · Khagga Mukkanti4 Received: 13 April 2020 / Revised: 30 June 2020 / Accepted: 6 July 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract We developed a novel, rapid, sensitive, and stability-indicating UHPLC method for quantification of Perindopril (PER), Amlodipine (AML), and their impurities in pharmaceutical formulations. The optimum chromatographic separation was achieved in gradient elution mode using Agilent SB C18 (50 × 3.0 mm, 1.8 μm) column. A buffer containing 0.1% perchloric acid and acetonitrile was used as a mobile phase component. The flow rate was 0.8 mL per minute and the detection wavelength at 215 nm was optimized. We also set an injection volume of 10 μL and the column thermostat at 60 °C. The findings were interesting: Resolution for PER, AML, and nine impurities is more than 1.5 for any pair of compounds. The proposed method is validated according to the ICH guidelines, and it is accurate, precise, linear, rugged, and robust. Specificity study proves the method efficiency in estimating PER, AML, and their related substances within the same run. The drug product was subjected to various stress degradation conditions and a significant amount of degradation in acid hydrolysis was observed. We proved the method robustness of chromatographic conditions by applying response surface methodology as a tool under a QbD approach and established the design space. This method is found to be stability-indicating and can be applied for analysis in quality control laboratories. Keywords Perindopril · Amlodipine · Validation · HPLC · Stability-indicating method · QbD · ANOVA
Introduction Perindopril (PER) is chemically known as (2S,3aS,7aS)1-[(2S)-2-[[(2S)-1-ethoxy-1-oxopentan-2-yl]amino] propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid. It is a non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with antihypertensive activity and in the Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10337-020-03936-6) contains supplementary material, which is available to authorized users. * T. S. S. Jagan Mohan [email protected] 1
Research and Development, JNTU, Kakinada 533003, Andhra Pradesh, India
2
Epione Labs Private LTD, Hyderabad, Telangana, India
3
Johnson and Johnson Private LTD, Mumbai, Maharashtra, India
4
Institute of Science and Technology, JNTUH, Kukatpally, Hyderabad, Telangana, India
hypertension therapy and stable coronary artery disease. PER is converted to its active form perindoprilat under hydrolysis [1]. Amlodipine (AML) is chemically known as 3-ethyl 5-methyl (4RS)-2-[(2-aminoethoxy) methyl]-4-(2chlorophenyl)-6-methyl-1,4-dihydropyridine-3, 5-dicarboxylate benzene sulfonate a synthetic dihydro pyridine with antihypertensive and anti
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