Analytical Method Development and Validation of Ticagrelor from Bulk and Formulation

Gupta, Anand; Jadhav, Vaishali; Jain, Ashish

doi:10.5958/2231-5691.2019.00022.4

Cited by 3 publications

(1 citation statement)

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“…Based on a comprehensive literature survey, there is no analytical method for the identification and quantitative determination of DPP derivative at such low levels in ticagrelor API and pharmaceutical formulations. Nevertheless, a literature review revealed that there are some HPLC methods (Bueno et al, 2017; Elmansi et al, 2020; Gupta et al, 2019; Joshy et al, 2016; Kelemen et al, 2019; Wingert et al, 2018; Yayé et al, 2015) which are available for the determination of assay and impurity profiling in ticagrelor. In addition, there are some LC–MS/MS methods (Danielak et al, 2019; Kelemen et al, 2019; Kumar et al, 2016; Pandya et al, 2016; Xu et al, 2019; Yayé et al, 2015) which are available for impurity profiling in ticagrelor.…”

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confidence: 99%

Development and validation of LC–QTOF–MS/MS method for the identification and determination of low levels of a genotoxic impurity, 4,6‐dichloro‐5‐nitro‐2‐(propylthio)pyrimidine in ticagrelor API

Moorthy

Ali

Reddy

2022

Biomedical Chromatography

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The foremost objective of the present study was to develop and validate a new LC-QTOF-MS/MS method for the identification and quantitative determination of 4,6-dichloro-5-nitro-2-(propylthio)pyrimidine (DPP) genotoxic impurity through the derivatization process in ticagrelor active pharmaceutical ingredient (API). Owing to the low response of DPP at the specification level, DPP was converted to 4,6-dibenzylamino-5-nitro-2-(propylthio)pyrimidine (DPP derivative) by addition of benzyl amine, then analyzed using mass spectrometry with a time-of-flight analyzer, and good separation was accomplished under the experimental conditions described.The effective separation of DPP derivative was achieved using an Acquity UPLC BEH C 18 reverse-phase column (100 Â 4.6 mm Â 1.7 μm) with an isocratic program with mobile phase A as 0.1% formic acid in milli Q water and mobile phase B as acetonitrile in the ratio of 20:80 v/v. The flow rate was maintained as 0.4 ml/min, the injection volume was 2 μl, the autosampler temperature was 5 C, the column oven temperature was ambient and the run time was 6.0 min. The diluent used was 0.2% benzyl amine in water and acetonitrile in the ratio of 30:70 v/v. The retention time of the DPP derivative was 2.87 min. The limit of detection and limit of quantification were 0.03 and 0.08 ppm, respectively. The DPP derivative was linear from 1.68 to 12.78 ppm with R 2 of 0.9958. Thus, the developed method is valid for the identification and quantitative determination of DPP derivative in ticagrelor API. K E Y W O R D S 4,6-dibenzylamino-5-nitro-2-(propylthio)pyrimidine (DPP derivative), genotoxic impurity, LC-ESI-QTOF-MS/MS, ticagrelor, time-of-flight analyzer 1 | INTRODUCTION Ticagrelor is an antiplatelet agent used to thin the blood in patients with acute coronary syndromes (Danielak et al., 2018). It inhibits platelet aggregation in coronary blood vessels and reduces cardiovascular death and heart attack by preventing the formation of new blood clots (

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Section: Introductionmentioning

confidence: 99%

Development and validation of LC–QTOF–MS/MS method for the identification and determination of low levels of a genotoxic impurity, 4,6‐dichloro‐5‐nitro‐2‐(propylthio)pyrimidine in ticagrelor API

Moorthy

Ali

Reddy

2022

Biomedical Chromatography

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UV Spectrophotometric and HPLC Method for Quantification of Ticagrelor in Bulk and Tablet Dosage Form

Bairam¹,

Tatapudi²,

Gajji³

et al. 2022

AJPA

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The aim of the present investigation was to develop, validate and compare a UV spectrophotometric and a high performance liquid chromatography method for estimating Ticagrelor in bulk and tablet dosage form. Spectrophotometry and high performance liquid chromatography were carried out using standard instrumental parameters, which were optimized. Both methods were validated in terms of linearity, accuracy, precision, robustness, ruggedness and stability according to the ICH guidelines. The optimized ratio of mobile phase in high performance liquid chromatography under low pressure gradient mode was 30:70 % v/v of acetonitrile:glacial acetic acid 1 % , which provide a sharp peak with a short retention time of 3.910 minutes. In UV spectrophotometric analysis iso-propyl alcohol as a solvent gave adequate molar absorptivity at a λmax of 306 nm. Results indicated that both UV spectrophotometric and high performance liquid chromatography methods were linear, precise, accurate, rugged and robust with RSD values less than 2 % and percent recovery was within the standard limits (90-110 %). Both the methods were found to be statistically non-significant at 95 % confidence intervals (p<0.05) with respect to each other. The proposed methods were found to be highly effective and could be used for quantification of Ticagrelor in bulk and a tablet formulations for routine analysis.

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A Review on Development of Stability Indicating Analytical Methods for drugs in Bulk and Pharmaceutical Dosage Form

Khaire

Pawar

2022

AJPA

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High performance liquid chromatography (HPLC) is an important analytical tool in analyzing drug stability. HPLC methods should be able to separate, detect, and quantify the various drug-related degradants. Forced degradation studies (chemical and physical stress testing) of new chemical entities and drug products are essential to help develop and demonstrate the specificity of such stability-indicating methods. In addition to demonstrating specificity, forced degradation studies can be used to determine the degradation pathways and degradation products of the APIs that could form during storage, and facilitate formulation development, manufacturing, and packaging. ICH guidelines demonstrate certain degradation conditions like light, oxidation, dry heat, acidic, basic, hydrolysis etc. ICH Q1A, QIB and Q2B exemplify the forced degradation studies. This review overviews the approaches and trends that are used in forced degradation studies.

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Analytical Method Development and Validation of Ticagrelor from Bulk and Formulation

Cited by 3 publications

References 0 publications

Development and validation of LC–QTOF–MS/MS method for the identification and determination of low levels of a genotoxic impurity, 4,6‐dichloro‐5‐nitro‐2‐(propylthio)pyrimidine in ticagrelor API

Development and validation of LC–QTOF–MS/MS method for the identification and determination of low levels of a genotoxic impurity, 4,6‐dichloro‐5‐nitro‐2‐(propylthio)pyrimidine in ticagrelor API

UV Spectrophotometric and HPLC Method for Quantification of Ticagrelor in Bulk and Tablet Dosage Form

A Review on Development of Stability Indicating Analytical Methods for drugs in Bulk and Pharmaceutical Dosage Form

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