抗病毒药物帕拉米韦:杂质的降解和鉴定及高效液相色谱-质谱法的认可。

IF 1.7 4区 农林科学 Q3 CHEMISTRY, ANALYTICAL
Thulaseedhar Alumuri, Karuna Sree Merugu, L A Amarababu Namburi, Aravınd Kurnool, Arunachalam SaravanaVadivu, Selvakumar Balasubramanian
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引用次数: 0

摘要

背景:Peramivir是一种神经氨酸酶抑制剂,作为流感神经氨酸酶的过渡状态类似物,抑制感染细胞中新病毒的形成,已被批准用于静脉注射。目的:建立高效液相色谱法鉴别抗病毒药物帕拉米韦降解产物的方法。方法:本文报道了帕拉米韦经酸、碱、过氧化物、热和光解降解后形成的化合物的鉴定。在毒理学水平上,设计了一种分离和测定帕拉米韦的技术。结果:建立了一种灵敏可靠的液相色谱-串联质谱法定量测定帕拉米韦及其杂质的方法,并经验证符合国际协调理事会(ICH)的建议。提议的方案在50-750µg/mL范围内。相对标准偏差小于2.0%,回收率为98.36 ~ 102.57%。在研究范围内,各杂质的线性关系良好,相关系数均在0.999以上。污染物的定量分析表明,该方法在低水平下效率高。结论:鉴于其降解产物的分离能力,在常规分析和稳定性研究中,定量分析可用于检测和定量帕拉米韦原料药中已知和未知的杂质和降解物。在过氧化和光解降解研究中没有发现明显的降解。重点:建立了高效液相色谱法,并进行了测试,以分析帕拉米韦中杂质在ICH建议的应激条件下降解的行为。Peramivir在过氧化和光解条件下是稳定的,但在酸、碱和热应力条件下不稳定或可降解。所开发的方法非常精确,线性,准确,坚固耐用。因此,该技术有潜力用于药物生产过程中的常规杂质分析以及帕拉米韦的稳定性分析。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
An Antiviral Drug-Peramivir: Degradation and Identification of Impurities and the Endorsement of an HPLC-MS Method.

Background: Peramivir is a neuraminidase inhibitor that serves as a transition state analogue for influenza neuraminidase, inhibiting the formation of new viruses in infected cells, and has been approved for intravenous administration.

Objective: To validate an HPLC method used to identify the degraded products of the antiviral drug peramivir.

Methods: Herein, we report the identification of compounds formed after the degradation of peramivir through acid, alkali, peroxide, thermal, and photolytic degradation. At the level of toxicology, a technique was devised for the isolation and measurement of peramivir.

Results: A sensitive and reliable LC-tandem mass spectrometry technique for the quantitative measurement of Peramivir and its impurities was developed and verified in order to comply with the recommendations made by the International Council for Harmonisation (ICH). The proposed protocol was in the 50-750 µg/mL range. Relative Standard Deviation values of less than 2.0% indicated good recovery in the range of 98.36-102.57%. Within the studied range, the calibration curves demonstrated good linearity and, in addition, the fitting of correlation coefficient was more than 0.999 for every impurity. Quantitative analysis of contaminants revealed the high efficiency at a low level.

Conclusion: Given its ability to separate degradation products, quantitative analysis is used to detect and quantify known and unknown impurities and degradants in the peramivir drug substance during routine analysis and stability studies. No significant degradation was found in peroxide and photolytic degradation studies.

Highlights: An HPLC method was developed and put to the test in order to analyze the behavior of the impurities of peramivir as they degraded when subjected to the stress conditions suggested by the ICH. Peramivir was found to be stable under peroxide and photolysis conditions but not stable or degradable when exposed to the acid, base, and thermal stress conditions. The method developed was extremely precise, linear, accurate, robust, and rugged. As a result, this technology has the potential to be used in the medication production process for regular impurity analysis as well as for the stability analysis of peramivir.

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来源期刊
Journal of AOAC International
Journal of AOAC International 医学-分析化学
CiteScore
3.10
自引率
12.50%
发文量
144
审稿时长
2.7 months
期刊介绍: The Journal of AOAC INTERNATIONAL publishes the latest in basic and applied research in analytical sciences related to foods, drugs, agriculture, the environment, and more. The Journal is the method researchers'' forum for exchanging information and keeping informed of new technology and techniques pertinent to regulatory agencies and regulated industries.
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