Analytical quality by design (AQbD) approach for the simultaneous quantification of FDC in a cardiovascular drug by RP-HPLC method

IF 3 Q2 PHARMACOLOGY & PHARMACY

Future Journal of Pharmaceutical Sciences Pub Date : 2026-04-28 DOI:10.1186/s43094-026-00985-w

Varsha Thorat, Sudhakar Alave, Vijay Bagul

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Abstract

Background

A sustainable and stability-indicating reversed-phase high-pressure liquid chromatography (RP-HPLC) method has been developed for the simultaneous estimation of chlorthalidone (CHL), Amlodipine (AML), and olmesartan medoxomil (OLM) in a combined cardiovascular dosage form by implementing an Analytical Quality by Design (AQbD) approach.

Methods

The RP-HPLC system employed a Sunniest C18 column (150 mm × 4.6 mm, 5.0 μm). The mobile phase consisted of 0.1% triethylamine in water (pH 2.4) and ethanol in a ratio of (65:35 v/v). At a flow rate of 1.5 mL/min. Detection was carried out at 245 nm using a photodiode array detector. Method optimization was performed using a Central composite design (CCD) under the AQbD framework. Forced degradation studies were conducted under acid, base, oxidative, thermal, and photolytic conditions to assess the method’s stability-indicating capability.

Results

The method showed good linearity in the 50–150% of test concentration with correlation coefficients (r²) exceeding 0.99 for all analytes. The method precision was found 98.9% for CHL and 101.4% for both AML and OLM. Forced degradation studies confirmed the method’s ability to resolve the active pharmaceutical ingredients from their degradation products. Well-separated, spectrally pure peaks were obtained for all analytes under all stress conditions, as confirmed by peak purity values greater than 0.950, indicating no interference from degradation products. The method demonstrated accuracy, precision, specificity, robustness as per the International Conference on Harmonization guidelines. Environmental sustainability was evaluated with GAPI (77), AMGS123, AGREEprep (0.69), and AGREE (0.81) scores, confirming its eco-friendly nature.

Conclusions

The integrated approach reduced solvent consumption, waste generation, and energy usage, supporting sustainable analysis. The method, validated as per ICH Q2(R2) guidelines, exhibited excellent linearity, precision, accuracy, specificity, robustness, and ruggedness. Forced degradation studies confirmed its stability-indicating capability. The present study highlights the need for incorporating antioxidants and implementing precautions against acidic and alkaline degradation, along with adopting proper packaging and storage strategies to enhance the stability of CHL, OLM, and AML in formulations prone to degradation..

Graphical abstract

The alternative text for this image may have been generated using AI.

Abstract Image

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反相高效液相色谱法同时定量心血管药物中FDC的质量设计分析方法

背景：建立了一种持续稳定的反相高压液相色谱（RP-HPLC）方法，通过设计分析质量（AQbD）方法同时测定心血管联合制剂中氯噻酮（CHL）、氨氯地平（AML）和奥美沙坦美多索米（OLM）的含量。方法反相高效液相色谱柱为Sunniest C18 （150 mm × 4.6 mm, 5.0 μm）。流动相为0.1%的三乙胺水溶液（pH 2.4）和乙醇（65:35 v/v）。流速为1.5 mL/min。使用光电二极管阵列检测器在245 nm处进行检测。在AQbD框架下，采用中心复合设计（CCD）对方法进行优化。在酸、碱、氧化、热和光解条件下进行了强制降解研究，以评估该方法的稳定性指示能力。结果该方法在50 ~ 150%的检测浓度范围内线性良好，相关系数（r2）均大于0.99。CHL的精密度为98.9%，AML和OLM的精密度为101.4%。强制降解研究证实了该方法从其降解产物中分离活性药物成分的能力。在所有的应力条件下，所有的分析物都得到了分离良好、光谱纯净的峰，峰的纯度值大于0.950，表明没有降解产物的干扰。该方法的准确性，精密度，特异性，鲁棒性符合国际协调会议的指导方针。采用GAPI（77）、AMGS123、AGREEprep（0.69）和AGREE（0.81）评分对环境可持续性进行评价，确认了其生态友好性。结论综合方法减少了溶剂消耗、废物产生和能源使用，支持可持续分析。该方法根据ICH Q2（R2）指南进行验证，具有良好的线性、精密度、准确度、特异性、稳健性和耐用性。强迫退化研究证实了它的稳定性指示能力。目前的研究强调了加入抗氧化剂和实施防止酸性和碱性降解的预防措施的必要性，以及采用适当的包装和储存策略，以提高CHL， OLM和AML在易于降解的配方中的稳定性。

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来源期刊

Future Journal of Pharmaceutical Sciences PHARMACOLOGY & PHARMACY-

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0.00%

发文量

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.