利用廉价的单四极杆质谱仪分析亚硝胺药物相关杂质的实用 HPLC-MS 方法。

IF 3.8 2区化学 Q1 BIOCHEMICAL RESEARCH METHODS

Journal of Chromatography A Pub Date : 2024-09-25 DOI:10.1016/j.chroma.2024.465399

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引用次数: 0

摘要

亚硝胺药物物质相关杂质（NDSRIs）通常采用高效液相色谱法（HPLC）和质谱法（MS）检测进行分析。由于灵敏度要求较高，通常使用高分辨率 MS 或 MS/MS。然而，这种方法很难在供应现场进行常规分析。在此，我们报告了一种系统方法，该方法利用 QDa 等廉价的单四极 MS 仪器，开发并验证了一种实用、稳健且用户友好的 NDSRIs 分析方法。我们以 7-亚硝基-3-(三氟甲基)-5,6,7,8-四氢-[1,2,4] 三唑并[4,3-a] 吡嗪（NTTP）为例，演示了方法的开发过程。通过优化高效液相色谱和质谱参数，我们开发出了一种简单的高效液相色谱-质谱方法，该方法具有分析 NTTP 所需的特异性和灵敏度，且易于在分析实验室中实施。该方法的定量限为 0.5 纳克/毫升，相当于 5 毫克/毫升西他列汀的 0.1 ppm。该方法已成功通过 ICH 指南的验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

A practical HPLC-MS method for the analysis of nitrosamine drug substance related impurities using an inexpensive single quadrupole mass spectrometer

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A practical HPLC-MS method for the analysis of nitrosamine drug substance related impurities using an inexpensive single quadrupole mass spectrometer

Nitrosamine drug substance related impurities (NDSRIs) are often analyzed using high performance liquid chromatography (HPLC) with mass spectrometry (MS) detection. Due to high sensitivity requirements, high resolution MS or MS/MS is commonly used. However, it is difficult to implement this type of method for routine analysis at a supply site. Herein, we report a systematic approach to develop and validate a practical, robust, and user-friendly method for the analysis of NDSRIs using an inexpensive single quadrupole MS instrument such as QDa. We used 7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro- [1,2,4] triazolo [4,3-a] pyrazine (NTTP) as an example to demonstrate the method development process. By optimizing the HPLC and MS parameters, we were able to develop a simple HPLC-MS method that provides the desired specificity and sensitivity for the analysis of NTTP and can be easily implemented in an analytical lab. The limit of quantitation is 0.5 ng/mL, corresponding to 0.1 ppm with respect to 5 mg/mL sitagliptin. The method has been successfully validated per ICH guidelines.

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来源期刊

Journal of Chromatography A 化学-分析化学

CiteScore

7.90

自引率

14.60%

发文量

742

审稿时长

45 days

期刊介绍： The Journal of Chromatography A provides a forum for the publication of original research and critical reviews on all aspects of fundamental and applied separation science. The scope of the journal includes chromatography and related techniques, electromigration techniques (e.g. electrophoresis, electrochromatography), hyphenated and other multi-dimensional techniques, sample preparation, and detection methods such as mass spectrometry. Contributions consist mainly of research papers dealing with the theory of separation methods, instrumental developments and analytical and preparative applications of general interest.