Pharmaceutical Impurities and Their Regulatory Aspects with a Special Focus on Genotoxic Impurities

International Journal Of Pharmaceutical Research And Allied Sciences, Journal Year: 2024, Volume and Issue: 13(2), P. 1 - 15

Published: Jan. 1, 2024

Language: Английский

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Rapid-Response Nitrite Probes: Intramolecular Griess Reaction for Nitrite Detection at Picogram Level

Organic Process Research & Development, Journal Year: 2023, Volume and Issue: 27(10), P. 1820 - 1826

Published: Sept. 8, 2023

Nitrite is abundantly used not only in the food industry but also various chemical reactions such as diazotization to furnish azo-dye compounds and Sandmeyer reaction. When a secondary amine presence of nitrite, residual levels nitrite ions can potentially form corresponding N-nitrosamines, many which are known be carcinogenic. The carcinogenicity concerns with N-nitrosamines resulted worldwide recalls numerous marketed pharmaceutical products since 2018. Therefore, assay critical part N-nitrosamine risk assessment, components present drug including substance excipients potential source ions. While ion chromatography serves primary analytical tool for assay, leveraging Griess reaction shows several benefits over chromatography, includes rapid visible responses well flexibility sample preparations organic solvent. In order simplify method enhance reactivity toward ion, series probe molecules was designed synthesized. Upon exposure molecular probes undergo followed by intramolecular cyclization benzo[c]cinnoline, elicits dramatic absorption emission changes signal readout assay. depends on nucleophilicity electron-withdrawing/donating properties substituents molecules. Among molecules, comparative kinetic studies revealed that para-sulfonamide-substituted molecule (probe 1) has highest no-detectable side With 1, validation performed two representative excipients, microcrystalline cellulose dicalcium phosphate dihydrate, demonstrated excellent accuracy, linearity, precision, multilevel spike/recovery very low detection limit (sub-parts-per-billion level) when coupled fluorescence detector. This new offers limits wide terms preparation higher composition Such solvent choice enables broader application any API, process intermediates, excipients.

Language: Английский

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Assessment and Control of Organic Impurities in Medicinal Products: A Review

The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products Regulatory Research and Medicine Evaluation, Journal Year: 2024, Volume and Issue: 14(2), P. 217 - 227

Published: April 5, 2024

INTRODUCTION. The determination of impurities is a key requirement for the quality assessment medicines because can significantly impact and therapeutic effectiveness. Pharmacopoeias are most important scientific methodological guidelines manufacturers developing medicinal product specifications regulators assessing these as part registration dossiers. Therefore, it essential to harmonise national international approaches impurities. AIM. This study aimed analyse summarise pharmacopoeial requirements control, evaluation, identification organic in medicines. DISCUSSION. authors compared control small-molecule set forth pharmacopoeias International Council Harmonisation Technical Requirements Medicinal Products Medical Use (ICH) Eurasian Economic Union (EAEU). comparison highlighted differences current that require further harmonisation existing regulatory documentation. Additionally, this analysed popularity, advantages, disadvantages different options determining two-component combination products (i.e. identified and/or unidentified one or each active substances). analysis demonstrated need nitrosamines genotoxic use selective highly sensitive chromatographic methods. CONCLUSIONS. When drafting monographs products, experts should consider general approach EAEU pharmacopoeia regulations ICH Q3B guideline. recommends process-related substances not be controlled at level. distinguish degradation from Impurities determined substance ensure safety fixed products. Priorities improving include using reference standards acknowledging necessity impurity quantification.

Language: Английский

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Control of N-nitrosamine impurities in drug products: Progressing the current CPCA framework and supporting the derivation of robust compound specific Acceptable Intakes

Regulatory Toxicology and Pharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 105762 - 105762

Published: Dec. 1, 2024

Language: Английский

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An Overview and Discussion of Azido Impurities and their Risk Assessments in Drug Substances and Drug Products

Asian Journal of Applied Chemistry Research, Journal Year: 2023, Volume and Issue: 13(4), P. 20 - 30

Published: May 30, 2023

Azido impurities are known to be mutagenic and carcinogenic. A small exposure these may lead cancer. These formed get incorporated into drug substances or products through reagents, catalysts, solvents, raw materials used in the process of manufacturing substances. Various regulatory authorities have published press releases notices regarding control with interim limit. can avoided by taking precautions during products. The methods identify quantify require highly sensitive instruments such as LCMS/MS GCMS, which detect a trace level within given validated according various guidelines. Liquid chromatography, along mass detector, is mostly for their determination.

Language: Английский

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Reactivity-based detection of nitrite ion: Rapid colorimetric and fluorometric response down to nM level

Tetrahedron Letters, Journal Year: 2024, Volume and Issue: 143, P. 155114 - 155114

Published: May 24, 2024

Language: Английский

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