Sustainable Stability Analysis of Vibegron: A Novel Chromatographic Method Development and Validation

IF 1.3 4区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Chromatographia Pub Date : 2025-08-18 DOI:10.1007/s10337-025-04430-7

Nidhi Vadnere, Mital Patel

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引用次数: 0

Abstract

A stability-indicating high-performance liquid chromatographic (HPLC) method for Vibegron (VBG) was developed and validated based on the analytical quality-by-design (AQbD) concept. Screening of critical factors were studied using risk assessment, followed by Plackett–Burman design, and optimization of critical factors were done using an I-optimal response surface design. The optimized chromatographic conditions include a Kromasil Classic C18 column (250 × 4.6 mm, 5 µm) and a mobile phase consisting of acetonitrile (A) and 10 mM ammonium acetate buffer pH adjusted to 4.5 with trifluoroacetic acid (B); in a ratio of (A:B; 46:54 v/v) ratio, at a flow rate of 0.8 mL/min, with a detection wavelength of 248 nm. The method has been validated as per ICH guidelines and demonstrated linearity (R² > 0.997), precision (% RSD < 2), and accuracy (99.97 ± 1.61% recovery). VBG was found to be sensitive during stress testing under various environmental conditions, including hydrolytic, oxidative, thermal, and photolytic stress. A total of 18 degradation products were separated, identified, and quantified using the developed method. The method's sustainability was assessed using the Whiteness assessment via the RGB 12 algorithm, the Analytical GREEness Tool (AGREE), the Complex Green Analytical Procedure Index, and the Blue Applicability Index, ultimately confirming that it is both green and practical. The developed method can be applied in pre-formulation studies, quality control, and pharmacovigilance.

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Vibegron的可持续稳定性分析：一种新的色谱方法的开发和验证

基于分析质量设计（AQbD）的概念，建立了一种稳定性指示的Vibegron （VBG）高效液相色谱法。采用风险评估法筛选关键因素，然后采用Plackett-Burman设计，采用i -最优响应面设计对关键因素进行优化。优化的色谱条件为：Kromasil Classic C18色谱柱（250 × 4.6 mm, 5µm），流动相为乙腈(a)和10 mm醋酸铵缓冲液（pH调至4.5，三氟乙酸(B)）；以（a:B; 46:54 v/v）比，流速为0.8 mL/min，检测波长为248 nm。方法按照ICH指南进行验证，线性（R2 > 0.997），精密度（% RSD < 2），准确度（99.97±1.61%）。在各种环境条件下，包括水解、氧化、热和光解胁迫下，VBG都是敏感的。采用该方法对18种降解产物进行了分离、鉴定和定量分析。通过RGB 12算法、分析绿色工具（AGREE）、复杂绿色分析程序指数和蓝色适用性指数对该方法的可持续性进行了白度评估，最终确认了该方法既环保又实用。该方法可用于制剂前研究、质量控制和药物警戒。

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来源期刊

Chromatographia 化学-分析化学

CiteScore

3.40

自引率

5.90%

发文量

103

审稿时长

2.2 months

期刊介绍： Separation sciences, in all their various forms such as chromatography, field-flow fractionation, and electrophoresis, provide some of the most powerful techniques in analytical chemistry and are applied within a number of important application areas, including archaeology, biotechnology, clinical, environmental, food, medical, petroleum, pharmaceutical, polymer and biopolymer research. Beyond serving analytical purposes, separation techniques are also used for preparative and process-scale applications. The scope and power of separation sciences is significantly extended by combination with spectroscopic detection methods (e.g., laser-based approaches, nuclear-magnetic resonance, Raman, chemiluminescence) and particularly, mass spectrometry, to create hyphenated techniques. In addition to exciting new developments in chromatography, such as ultra high-pressure systems, multidimensional separations, and high-temperature approaches, there have also been great advances in hybrid methods combining chromatography and electro-based separations, especially on the micro- and nanoscale. Integrated biological procedures (e.g., enzymatic, immunological, receptor-based assays) can also be part of the overall analytical process.