Systematic QbD-Assisted RP-HPLC Method Development for Impurity Analysis of Efonidipine Hydrochloride Ethanolate, Chlorthalidone, and Telmisartan in a Single Pill: A Novel Fixed Dose Combination

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmaceutical Innovation Pub Date : 2026-09-22 DOI:10.1007/s12247-026-11042-7

Anil Gadhe, Atmaram Pawar, Vikram Gharge, Balasaheb Jadhav, Vikas Mohite

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引用次数: 0

Abstract

Purpose

Efonidipine Hydrochloride Ethanolate, Chlorthalidone, Telmisartan, and their associated impurities, Efonidipine Related Compound A and Chlorthalidone Related Compound A, in a fixed-dose combination tablet formulation were developed and validated using an RP-HPLC approach.

Methods

Method development and optimization was done using a Quality by Design methodology supported by Design of Experiments to ensure systematic optimization and dependable chromatographic performance. Buffer pH and mobile phase composition were determined to be crucial technique parameters based on risk assessment, and a central composite design was used to optimize them. They were statistically assessed for their impact on retention durations of the analytes, resolution between Chlorthalidone and Chlorthalidone Related Compound A, and crucial analytical responses between Telmisartan and Efonidipine Related Compound A.

Results

With correlation coefficients (R²) falling within the range, predictive models demonstrated great reliability. Gradient elution with phosphate buffer, acetonitrile, and methanol utilizing a Photodiode Array detector produced the best separation. Results demonstrated adequate specificity, accuracy, linearity, precision, sensitivity, and robustness after the method was validated in accordance with ICH criteria. Efonidipine Related Compound A and Chlorthalidone Related Compound A were fully validated for their ability to quantify active pharmaceutical ingredients. Resultant separation of degradation products, analyte, and impurity peaks was confirmed by conducting forced degradation studies under various saturation parameters, showing the stability-indicating nature of the method.

Conclusion

The developed method can serve for stability studies, impurity profiling, and routine quality control of this triple-drug combination.

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qbd辅助的系统反相高效液相色谱法：一种新的固定剂量组合——盐酸埃福尼地平乙醇酸盐、氯噻酮和替米沙坦的杂质分析

目的采用反相高效液相色谱法对固定剂量联合片剂中埃福尼地平、氯噻酮、替米沙坦及其相关杂质埃福尼地平相关化合物A和氯噻酮相关化合物A进行验证。方法采用设计质量法和实验设计法进行方法开发和优化，以确保系统优化和可靠的色谱性能。在风险评估的基础上确定缓冲液pH和流动相组成为关键工艺参数，并采用中心组合设计对其进行优化。统计评估了它们对分析物的保留时间、氯噻酮与氯噻酮相关化合物A之间的分辨率以及替米沙坦与依福地平相关化合物A之间的关键分析响应的影响。结果相关系数（R²）在一定范围内，预测模型具有较高的可靠性。磷酸缓冲液、乙腈、甲醇梯度洗脱，光电二极管阵列检测器分离效果最佳。根据ICH标准对方法进行验证后，结果显示出足够的特异性、准确性、线性度、精密度、灵敏度和稳健性。对Efonidipine相关化合物A和Chlorthalidone相关化合物A进行了充分验证，以确定其定量活性药物成分的能力。通过在各种饱和度参数下进行强制降解研究，证实了降解产物、分析物和杂质峰的分离，显示了该方法的稳定性。结论该方法可用于该三联药的稳定性研究、杂质分析和常规质量控制。

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来源期刊

Journal of Pharmaceutical Innovation PHARMACOLOGY & PHARMACY-

CiteScore

3.70

自引率

3.80%

发文量

审稿时长

>12 weeks

期刊介绍： The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories: Materials science, Product design, Process design, optimization, automation and control, Facilities; Information management, Regulatory policy and strategy, Supply chain developments , Education and professional development, Journal of Pharmaceutical Innovation publishes four issues a year.