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不同分析技术检测 HIV-1 整合酶抑制剂:拉替拉韦、多替拉韦、艾维雷韦和比克替拉韦的综合评价。

Comprehensive Review on Different Analytical Techniques for HIV 1- Integrase Inhibitors: Raltegravir, Dolutegravir, Elvitegravir and Bictegravir.

机构信息

Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi, India.

Indian Pharmacopoeia Commission, Ministry of Health and Family Welfare, Ghaziabad, UP, India.

出版信息

Crit Rev Anal Chem. 2024;54(2):401-415. doi: 10.1080/10408347.2022.2080493. Epub 2022 May 26.

Abstract

The advent of HIV-Integrase inhibitors (IN) has marked a significant impact on the lives of HIV patients. Since the launch of the first anti retro-viral drug "Azidothymidine" to the recent advances of IN inhibitors, about 27.4 million people benefit by antiretroviral therapy (ART). The path had been challenging due to many crossroads, leading to the discovery of newer targets. One such recent ART target is Integrase. Use of Integrase inhibitors has surpassed the usage of all other ART owing to a strong barrier to resistance and have been reported to be the first-line therapy. Raltegravir, Elvitegravir, Dolutegravir and Bictegravir are US FDA approved IN inhibitors. The high usage of ART created an opportunity to study various analytical techniques for IN inhibitors. Hitherto, no review encompassing all IN inhibitors is presented. Herein, this review describes the analytical techniques employed for IN inhibitors estimation and quantification reported in the literature and official compendia. Literature suggests that most studies focus on LC-MS/MS and HPLC methods for drug estimation, and few reports suggest spectrophotometric, spectrofluorimetric and electrochemical methods. Furthermore, the review presents the techniques that describe the quantification of integrase drugs in various matrices. Although, antiretroviral drugs are extensively used but data suggests that limited studies have been conducted for determination of impurity profile and stability. This therefore, presents a scope to detect and validate impurities in order to meet ICH guidelines for their limits and further to improve the quality and safety of antiretroviral drugs.

摘要

HIV 整合酶抑制剂(IN)的出现对 HIV 患者的生活产生了重大影响。自第一个抗逆转录病毒药物“叠氮胸苷”问世到最近 IN 抑制剂的进展,约有 2740 万人受益于抗逆转录病毒治疗(ART)。由于存在许多交叉路口,导致发现了更新的目标,这条道路充满了挑战。最近的一种 ART 靶标就是整合酶。由于具有很强的耐药性障碍,整合酶抑制剂的使用已经超过了所有其他 ART 的使用,并已被报道为一线治疗药物。拉替拉韦、艾维雷格、度鲁特韦和比克替拉韦已获得美国食品和药物管理局(FDA)批准为 IN 抑制剂。ART 的广泛使用为研究各种 IN 抑制剂分析技术创造了机会。迄今为止,尚无涵盖所有 IN 抑制剂的综述。本文综述了文献和官方专著中报道的用于 IN 抑制剂评估和定量的分析技术。文献表明,大多数研究都集中在 LC-MS/MS 和 HPLC 方法用于药物评估,少数报告表明分光光度法、荧光光谱法和电化学方法。此外,该综述还介绍了用于描述整合酶药物在各种基质中定量的技术。尽管抗逆转录病毒药物广泛使用,但数据表明,对杂质谱和稳定性的测定研究有限。因此,这为检测和验证杂质提供了一个机会,以达到 ICH 关于杂质限度的指导原则,并进一步提高抗逆转录病毒药物的质量和安全性。

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