Elzayat Ehab M, Sherif Abdelrahman Y, Attwa Mohamed W, Altamimi Mohammad A
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
ACS Omega. 2024 Nov 1;9(45):45011-45024. doi: 10.1021/acsomega.4c04927. eCollection 2024 Nov 12.
Clinical trials revealed that pioglitazone (PGZ) and dapagliflozin (DGZ) not only maintain normal blood glucose levels but also reduce complications of diabetes mellitus. To meet the demand for simultaneous measurement of these drugs in fixed combinations, an optimized and green UPLC method is required. The present study utilized Design of Experiments (DoE) software to optimize analytical parameters for simultaneous drug analysis. The method was validated for its linearity, accuracy, and precision. Furthermore, the drug content was estimated in different pharmaceutical dosage forms. Finally, Analytical Greenness (AGREE) software was utilized to assess the environmental sustainability of the optimized UPLC method. Drugs were successfully separated using optimized conditions on the C18 Acquity BEH column (2.1 mm × 100 mm, 1.7 μm) at a temperature of 45 °C. The mobile phase consisted of ethanol and 9 mM ammonium formate buffer (43.7:56.3), with elution carried out at a flow rate of 0.246 mL/min. The optimized method showed excellent linearity ( > 0.999), accuracy (92.45-109.25%), and good precision (RSD < 6.27%) for both drugs. In addition, the optimized UPLC method was able to determine the drug content within the marketed pharmaceutical dosage form accurately. The developed UPLC method also prioritized eco-friendliness by using green solvents to minimize the negative impact on the environment. The green UPLC method provides a reliable and accurate approach to estimate PGZ and DGZ in a fixed diabetes treatment combination. It promotes sustainable lab practices and paves the way for analytical methods for new dose combinations.
临床试验表明，吡格列酮（PGZ）和达格列净（DGZ）不仅能维持正常血糖水平，还能降低糖尿病并发症。为满足对固定复方制剂中这些药物同时测定的需求，需要一种优化的绿色超高效液相色谱（UPLC）方法。本研究利用实验设计（DoE）软件优化同时药物分析的分析参数。该方法进行了线性、准确度和精密度验证。此外，还对不同药物剂型中的药物含量进行了测定。最后，利用分析绿色度（AGREE）软件评估优化后的UPLC方法的环境可持续性。在45℃温度下，使用优化条件在C18 Acquity BEH柱（2.1 mm×100 mm，1.7μm）上成功分离了药物。流动相由乙醇和9 mM甲酸铵缓冲液（43.7:56.3）组成，以0.246 mL/min的流速进行洗脱。优化后的方法对两种药物均显示出优异的线性（>0.999）、准确度（92.45 - 109.25%）和良好的精密度（RSD < 6.27%）。此外，优化后的UPLC方法能够准确测定市售药物剂型中的药物含量。所开发的UPLC方法还通过使用绿色溶剂优先考虑了生态友好性，以尽量减少对环境的负面影响。绿色UPLC方法为准确测定固定糖尿病治疗复方制剂中的PGZ和DGZ提供了一种可靠且准确的方法。它促进了可持续的实验室操作，并为新剂量组合的分析方法铺平了道路。
