Prajapati Pintu, Tailor Pratik, Shahi Abhinandan, Acharya Aneri, Shah Shailesh
Maliba Pharmacy College, Maliba Campus, Department of Quality Assurance, Bardoli-Mahuva Road, Tarsadi, Mahuva, Surat, 394 350 Gujarat, India.
J AOAC Int. 2022 Sep 6;105(5):1491-1501. doi: 10.1093/jaoacint/qsac056.
Numerous fixed-dose combinations (FDCs) of cilnidipine (CIL) with chlorthalidone (CLT) and azilsartan medoxomil (AZL) are used for the treatment of hypertension. Numerous reverse-phase high-pressure liquid chromatography (RP-HPLC) and high-performance thin-layer chromatography (HPTLC) methods have been reported in the literature for the estimation of FDCs of CIL. But no HPTLC method has been reported yet for synchronous estimation of multiple FDCs of CIL to save time, organic solvent, and cost of analysis. In the recent scenario of green chemistry, the minimum usage of organic solvent in the development of the chromatographic method is highly desirable for the safety of the environment and analysts.
Hence, a robust and green HPTLC method has been developed for the synchronous estimation of multiple FDCs of CIL using the analytical quality by design (AQbD) approach.
The chemometric tool was applied for the identification of the critical method variables (CMVs) and critical analytical attributes (CAAs) for the HPTLC method development. The design of experiments (DoE) was applied for the response surface analysis of identified CMVs and CAAs using the Box-Behnken design. The analytical design space and control strategy was framed for the lifecycle management of the HPTLC method.
The chromatographic separation was performed using silica gel G60 F254 as the stationary phase and toluene-ethyl acetate-methanol (6.5 + 2 + 1.5, v/v) as the mobile phase. The method was validated as per the International Council for Harmonization Q2 (R1) guideline. The developed method was applied for the synchronous estimation of multiple FDCs of CIL, and results were found in compliance with labeled claims.
The developed HPTLC method can be used as a green, economical, and rapid analytical tool for routine analysis and quality control of multiple FDCs of CIL in the pharmaceutical industry.
Development of a HPTLC method for synchronous estimation of multiple FDCs of CIL using the AQbD approach based on principles of chemometry and DoE. Application of the developed method for synchronous assay of multiple FDCs of CIL to save time, cost, and solvent for analysis.
西尼地平（CIL）与氯噻酮（CLT）及阿齐沙坦美洛昔酯（AZL）的多种固定剂量复方制剂（FDCs）用于治疗高血压。文献中已报道了许多反相高效液相色谱（RP - HPLC）和高效薄层色谱（HPTLC）法用于测定CIL的FDCs。但尚未见有HPTLC法用于同步测定CIL的多种FDCs以节省时间、有机溶剂和分析成本的报道。在绿色化学的当下，色谱方法开发中有机溶剂的最少使用量对于环境和分析人员的安全而言是非常可取的。
因此，已采用设计质量分析（AQbD）方法开发了一种稳健且绿色的HPTLC法用于同步测定CIL的多种FDCs。
将化学计量学工具应用于HPTLC方法开发中关键方法变量（CMVs）和关键分析属性（CAAs）的识别。采用Box - Behnken设计的实验设计（DoE）对已识别的CMVs和CAAs进行响应面分析。为HPTLC方法的生命周期管理构建了分析设计空间和控制策略。
使用硅胶G60 F254作为固定相，甲苯 - 乙酸乙酯 - 甲醇（6.5 + 2 + 1.5，v/v）作为流动相进行色谱分离。该方法按照国际协调理事会Q2（R1）指南进行了验证。所开发的方法用于同步测定CIL的多种FDCs，结果符合标签声称。
所开发的HPTLC方法可作为一种绿色、经济且快速的分析工具，用于制药行业中CIL多种FDCs的常规分析和质量控制。
基于化学计量学和DoE原理，采用AQbD方法开发用于同步测定CIL多种FDCs的HPTLC方法。所开发的方法用于同步测定CIL的多种FDCs，以节省分析时间、成本和溶剂。
