Identification, synthesis, and characterization of an unprecedented N-(2-carboxyethyl) adduct impurity in an injectable ganirelix formulation

IF 1.8 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Peptide Science Pub Date : 2023-12-22 DOI:10.1002/psc.3564

Rohit Jadav, Ramraj Kameriya, Saurav Chatterjee, Vinod Gour, Parva Purohit, Anupam Bandyopadhyay

引用次数: 0

Abstract

Ganirelix, a peptide-based drug used to treat female infertility, has been in high market demand, which attracted generic formulation. A hitherto unknown impurity of ganirelix was observed in our formulation process, which reached ~0.3% in 6 months and led to a detailed investigation of its structure. In-depth analysis of ESI-MS/MS data of this impurity coupled with an artificial intelligence prediction tool led to a highly unusual putative structure, that is, N-(2-carboxyethyl)-ganirelix (^NCE-GA), which was authenticated by chemical synthesis from ganirelix and NMR analysis and via corroborated HPLC and MS/MS data with the formulation-derived impurity.

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鉴定、合成和表征注射用加尼瑞克制剂中一种前所未有的 N-（2-羧乙基）加成杂质。

加尼瑞克（Ganirelix）是一种用于治疗女性不孕症的多肽类药物，市场需求量很大，因此吸引了仿制药的出现。在我们的制剂过程中发现了一种迄今未知的加尼瑞克杂质，在 6 个月内杂质含量达到 ~0.3%，因此对其结构进行了详细研究。通过对该杂质的 ESI-MS/MS 数据进行深入分析，并结合人工智能预测工具，得出了一种非常不寻常的推定结构，即 N-（2-羧乙基）-加尼瑞克（N CE-GA），并通过加尼瑞克的化学合成和 NMR 分析，以及与制剂衍生杂质相互印证的 HPLC 和 MS/MS 数据对该结构进行了验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Peptide Science 生物-分析化学

CiteScore

3.40

自引率

4.80%

发文量

审稿时长

1.7 months

期刊介绍： The official Journal of the European Peptide Society EPS The Journal of Peptide Science is a cooperative venture of John Wiley & Sons, Ltd and the European Peptide Society, undertaken for the advancement of international peptide science by the publication of original research results and reviews. The Journal of Peptide Science publishes three types of articles: Research Articles, Rapid Communications and Reviews. The scope of the Journal embraces the whole range of peptide chemistry and biology: the isolation, characterisation, synthesis properties (chemical, physical, conformational, pharmacological, endocrine and immunological) and applications of natural peptides; studies of their analogues, including peptidomimetics; peptide antibiotics and other peptide-derived complex natural products; peptide and peptide-related drug design and development; peptide materials and nanomaterials science; combinatorial peptide research; the chemical synthesis of proteins; and methodological advances in all these areas. The spectrum of interests is well illustrated by the published proceedings of the regular international Symposia of the European, American, Japanese, Australian, Chinese and Indian Peptide Societies.