基于分析质量设计(AQbD)的 RP-UPLC 方法的优化,用于测定散装和药物剂型中的 nivolumab 和 relatlimab

IF 3.4 Q2 PHARMACOLOGY & PHARMACY
Mohana Vamsi Nuli, Ramanjaneyulu Seemaladinne, Anil Kumar Tallam
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引用次数: 0

摘要

通过设计提高分析质量(AQbD)方法将通过设计提高质量(QbD)原则的应用扩展到分析程序生命周期的管理,包括方法创建、优化、验证和持续改进。AQbD 有助于创建稳健、可靠、精确和具有成本效益的分析程序。Opdualag™是Nivolumab和Relatlimab的复方制剂,Nivolumab和Relatlimab是阻断程序性死亡受体-1(PD-1)和淋巴细胞活化基因3(LAG-3)受体的抗体,用于治疗晚期黑色素瘤。这项研究旨在利用AQbD原理开发并验证一种反相超高效液相色谱(RP-UPLC)方法,以测定药品中的NLB和RTB。通过 Design-expert® 软件对色谱条件进行优化,采用了由三个因素组成的中央复合设计 (CCD),并将其分为五个不同的层次。构建了一个数学模型,并研究了三个独立因素,即流速 (X1)、流动相中甲醇的百分比 (X2) 和温度 (X3) 对保留时间 (Y1-2)、分辨率因子 (Y3)、理论平板 (Y4-5) 和拖尾因子 (Y6-7) 等反应的影响。软件确定了分离 NLB 和 RTB 的最佳色谱条件如下:流动相为 32.80%甲醇,流速为 0.272 mL/min,柱温为 29.42 ℃,紫外检测波长为 260 nm。NLB 和 RTB 的保留时间分别为 1.46 和 1.88 min。该方法的线性范围分别为 RTB 4-24 µg/mL 和 NLB 12-72 µg/mL。NLB和RTB的检出限(LOD)和定量限(LOQ)分别为0.89微克/毫升、2.69微克/毫升和0.15微克/毫升和0.46微克/毫升。NLB和RTB的日内和日间精密度相对标准偏差(%RSD)均低于2。 NLB和RTB的回收率分别为99.57%-100.43%和99.59%-100.61%。在强制降解研究中发现,这两种药物都容易发生氧化和光解降解。采用基于AQbD的方法,建立了一种简便、快速、准确、精确、特异、稳定的RP-UPLC方法,用于药物制剂中NLB及其RTB的定量分析。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Analytical quality by design (AQbD) based optimization of RP-UPLC method for determination of nivolumab and relatlimab in bulk and pharmaceutical dosage forms

Background

The Analytical Quality by Design (AQbD) methodology extends the application of Quality by Design (QbD) principles to the management of the analytical procedure life cycle, encompassing method creation, optimization, validation, and continuous improvement. AQbD assists in creating analytical procedures that are robust, reliable, precise, and cost-efficient. Opdualag™ is a combination of Nivolumab and Relatlimab, which are antibodies that block programmed death receptor-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) receptors, used to treat advanced melanoma. This work aims to develop and validate a reversed-phase ultra-performance liquid chromatography (RP-UPLC) method using AQbD principles to determine NLB and RTB in pharmaceutical products.

Results

A central composite design (CCD) comprising three factors arranged in five distinct levels was implemented via Design-expert® software to optimize the chromatographic conditions. A mathematical model was constructed and the effects of three independent factors namely flow rate (X1), percentage of methanol in the mobile phase (X2), and temperature (X3) on responses including retention time (Y1–2), resolution factor (Y3), theoretical plates (Y4–5), and tailing factor (Y6–7) were investigated. The software determined the optimal chromatographic conditions for the separation of NLB and RTB, which were as follows: 32.80% methanol in the mobile phase, 0.272 mL/min flow rate, 29.42 °C column temperature, and 260 nm UV detection. The retention time for NLB and RTB were 1.46 and 1.88 min, respectively. The method exhibited linearity across the concentration ranges of 4–24 µg/mL for RTB and 12–72 µg/mL for NLB. The limits of detection (LOD) and limit of quantification (LOQ) for NLB and RTB, respectively, were 0.89 µg/mL, 2.69 µg/mL and 0.15 µg/mL and 0.46 µg/mL. The percentage relative standard deviation (%RSD) of intraday and interday precision for NLB and RTB was below 2. The recovery percentages for NLB and RTB were determined to be 99.57–100.43% and 99.59–100.61%, respectively. Both drugs were found to be susceptible to oxidative and photolytic degradation in forced degradation studies.

Conclusions

Employing the AQbD-based methodology, a straightforward, fast, accurate, precise, specific, and stability-indicating RP-UPLC method has been established for the quantitative analysis of NLB and its RTB in pharmaceutical formulations.

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来源期刊
自引率
0.00%
发文量
44
审稿时长
23 weeks
期刊介绍: Future Journal of Pharmaceutical Sciences (FJPS) is the official journal of the Future University in Egypt. It is a peer-reviewed, open access journal which publishes original research articles, review articles and case studies on all aspects of pharmaceutical sciences and technologies, pharmacy practice and related clinical aspects, and pharmacy education. The journal publishes articles covering developments in drug absorption and metabolism, pharmacokinetics and dynamics, drug delivery systems, drug targeting and nano-technology. It also covers development of new systems, methods and techniques in pharmacy education and practice. The scope of the journal also extends to cover advancements in toxicology, cell and molecular biology, biomedical research, clinical and pharmaceutical microbiology, pharmaceutical biotechnology, medicinal chemistry, phytochemistry and nutraceuticals.
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