Establishment of validated stability indicating purity method based on the stress degradation behavior of gonadotropin-releasing hormone antagonist (ganirelix) in an injectable formulation using HPLC and LC-MS-QTOF.

IF 1.1 4区 化学 Q4 PHYSICS, ATOMIC, MOLECULAR & CHEMICAL
European Journal of Mass Spectrometry Pub Date : 2021-04-01 Epub Date: 2021-04-07 DOI:10.1177/14690667211005335
Kumarswamy Ummiti, J V Shanmukha Kumar
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引用次数: 3

Abstract

Stress study of a drug substance or pharmaceutical drug product provides a vision into degradation pathways and degradation products of the active pharmaceutical ingredient and helps in interpretation of the chemical structure of the degradation impurities. In the current study, Ganirelix active ingredient presented in the Orgalutran® was stressed with acidic and alkali hydrolysis, photolysis, thermal and oxidation conditions as per the guidelines of International Conference on Harmonization (ICH) Q1A (R2). Ganirelix was found to be labile under thermal and alkali hydrolytic stress conditions, while it was stable to acid hydrolytic, oxidative and photolytic stress. All degradation products were separated with a resolution > 1.5 on a C18 column (2.6 µm, 25 cm×4.6 mm) using a hydrophilic ion pair such as sodium perchlorate, at a concentration <0.04 M. In total, four major degradant impurities were found during stress study. These impurities were fractionated and desalted by flash chromatography for identification of chemical structures. LC-MS-QTOF analysis revealed that two degradation products are diastereomers of Ganirelix, one degradation product is a deamination compound and other degradation product result from the insertion of a new amino acid residue in the Ganirelix peptide sequence. The developed method is sensitive enough to quantify the related substances of Ganirelix at the 0.04% level with that of Ganirelix test concentration.

基于促性腺激素释放激素拮抗剂(ganirelix)在注射制剂中的应激降解行为,采用HPLC和LC-MS-QTOF建立了经过验证的稳定性指示纯度方法。
对原料药或药品的应力研究提供了对活性药物成分的降解途径和降解产物的认识,并有助于解释降解杂质的化学结构。在本研究中,根据国际协调会议(ICH) Q1A (R2)的指导方针,在Orgalutran®中提出的Ganirelix活性成分在酸碱水解、光解、热和氧化条件下进行了强调。甘尼瑞克在热和碱水解条件下不稳定,而在酸水解、氧化和光解条件下稳定。所有降解产物在C18柱(2.6µm, 25 cm×4.6 mm)上分离,分辨率> 1.5,使用亲水性离子对,如高氯酸钠,在一定浓度下
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来源期刊
CiteScore
2.40
自引率
7.70%
发文量
16
审稿时长
>12 weeks
期刊介绍: JMS - European Journal of Mass Spectrometry, is a peer-reviewed journal, devoted to the publication of innovative research in mass spectrometry. Articles in the journal come from proteomics, metabolomics, petroleomics and other areas developing under the umbrella of the “omic revolution”.
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