应用Plackett-Burman和Box-Behnken设计建立了一种灵敏、稳健的高效液相色谱法定量降血脂药物瑞舒伐他汀和苯甲多酸片剂

IF 3.4 Q2 PHARMACOLOGY & PHARMACY

Future Journal of Pharmaceutical Sciences Pub Date : 2025-05-26 DOI:10.1186/s43094-025-00814-6

Susmitha Aggarapu, Rajitha Galla, Neha Jabeen Shaik, Sai Jyothi Dasari

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引用次数: 0

摘要

设计分析质量方法是一种系统、科学的方法，用于开发可靠的分析程序。应用QbD原理建立稳定指示的高效液相色谱法定量瑞舒伐他汀和苯戊酸片剂，通过确定关键的方法参数和分析属性，提高了对方法的理解，保证了质量的一致性。方法采用两水平七因素Plackett-Burman设计筛选方法参数。基于Pareto排序分析，确定了%水溶液（%v/v）、缓冲液pH和流速（ml/min）为关键方法参数，瑞舒伐他汀和苯戊二酸的保留时间和分辨率为关键分析属性。采用两级三因素Box-Behnken设计进行优化。最终优化的方法采用Spursil C18色谱柱（5µm, 150 × 4.6 mm），流动相为15 mm醋酸铵缓冲液（pH 6.0）和乙腈（40:60%v/v），流速为1 mL/min，紫外检测波长为244 nm，运行时间为8 min。结果在上述条件下，瑞舒伐他汀和苯甲多酸的滞留时间分别为2.474 min和3.396 min。优化方法的验证遵循ICH Q2 （R1）指南，包括系统适用性、专属性、线性、准确度、精密度、检出限、定量限和鲁棒性评估。瑞舒伐他汀在0.8 ~ 4.0µg/mL范围内呈线性，苯甲醚酸在3.6 ~ 18µg/mL范围内呈线性。此外，使用AGREE软件对方法的绿色度进行评估，其得分为0.72，表明该方法符合绿色分析化学原则。结论建立的反相高效液相色谱法对瑞舒伐他汀和苯甲多酸片剂的含量测定具有灵敏度高、鲁棒性好等优点。使用Plackett-Burman和Box-Behnken设计促进了有效的优化，该方法符合ICH指南和绿色标准，确认其适用于质量控制实验室的常规分析。图形抽象

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Application of Plackett–Burman and Box–Behnken designs to develop a sensitive and robust HPLC method for quantifying hypolipidemic drugs, rosuvastatin and bempedoic acid in tablets

Background

Analytical quality by design approach is a systematic and scientific method for developing robust analytical procedures. Applying QbD principles in developing stability-indicating HPLC method for quantifying rosuvastatin and bempedoic acid in tablets enhances method understanding by identifying critical method parameters and analytical attributes, ensuring consistent quality.

Method

A two-level seven-factor Plackett–Burman design was employed to screen method parameters. Based on Pareto ranking analysis, the % aqueous (%v/v), buffer pH, and flow rate (ml/min) were identified as critical method parameters, while the retention times of rosuvastatin and bempedoic acid and resolution were selected as critical analytical attributes. Optimization was conducted using a two-level three-factor Box–Behnken design. The final optimized method utilized a Spursil C18 column (5 µm, 150 × 4.6 mm) with a mobile phase consisting of 15 mM ammonium acetate buffer (pH 6.0) and acetonitrile (40:60%v/v), a flow rate of 1 mL/min, and UV detection at 244 nm with an 8-min run time.

Results

Under the above conditions, rosuvastatin and bempedoic acid had retention times of 2.474 min and 3.396 min, respectively. Validation of the optimized method followed ICH Q2 (R1) guidelines and included system suitability, specificity, linearity, accuracy, precision, detection limit, quantitation limit, and robustness assessments. Linearity was observed in the range of 0.8–4.0 µg/mL for rosuvastatin and 3.6–18 µg/mL for bempedoic acid. Additionally, the greenness of the method was evaluated using AGREE software, which provided a score of 0.72, indicating compliance with Green Analytical Chemistry principles.

Conclusion

The developed RP-HPLC method is both sensitive and robust for the quantification of rosuvastatin and bempedoic acid in tablet formulations. The use of Plackett–Burman and Box–Behnken designs facilitated efficient optimization, and the method meets ICH guidelines and greenness criteria, confirming its suitability for routine analysis in quality control laboratories.

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来源期刊

Future Journal of Pharmaceutical Sciences PHARMACOLOGY & PHARMACY-

自引率

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.