Nabil Mona, Ahmed Dina A, Abbas Samah S, Lotfy Hayam M, Marzouk Hoda M
Faculty of Pharmacy, Cairo University, El-Kasr El-Aini Street, Cairo, 11562, Egypt.
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Future University in Egypt, Cairo, 11835, Egypt.
BMC Chem. 2025 Jul 3;19(1):187. doi: 10.1186/s13065-025-01559-2.
The introduction of new pharmaceutical formulations necessitates the development of a trustworthy analytical approach capable of quantifying active ingredients in various quality control procedures. A fixed dosage combination of carvedilol (CAR) and hydrochlorothiazide (HCT) has been introduced to treat hypertension with potential recommendation for diabetic patients. Ahigh-performance liquid chromatographic methodology, designed to be ecologically sustainable while maintaining high precision and accuracy, was established. This approach can simultaneously determine both drugs in their pure forms, and dosage form, along with separation and quantification of potential hydrochlorothiazide related impurities; salamide (DSA) and chlorothiazide (CT). Successful separation was performed using YMCTriart-Phenyl analytical column via gradient elution employing 0.1% formic acid alongside ethanol at a flow rate of 1.0 mL/min, coupled with photodiode array detection at 254.0 nm. Linearity was obtained across the concentration ranges of 0.1 to 100.0 µg/mL for HCT and CAR and 0.05 to 10.0 µg/mL for DSA and CT. The suggested chromatographic methodology can estimate HCT and CAR in different real samples. Additionally, it facilitates the concurrent monitoring of their dissolution profiles. The studied method's performance was validated in adherence to the guidelines set by the International Conference on Harmonization (ICH). Moreover, its ecological sustainability as well as applicability profile was further affirmed via diverse greenness, blueness, and whiteness assessment tools and compared among official and other reported procedures. In addition, the recently introduced Carbon Footprint Reduction Index tool has been implemented to assess the suggested method with an emphasis on estimating CO emissions. In general, the suggested methodology proves to be effective for conducting the quality control examination of raw forms and commercially accessible preparations.
新药物制剂的引入需要开发一种可靠的分析方法，以便在各种质量控制程序中对活性成分进行定量分析。已引入卡维地洛（CAR）和氢氯噻嗪（HCT）的固定剂量组合来治疗高血压，并可能推荐给糖尿病患者。建立了一种高性能液相色谱方法，该方法在保持高精度和准确性的同时，设计为具有生态可持续性。该方法可以同时测定纯形式和剂型中的两种药物，以及潜在的氢氯噻嗪相关杂质；水杨酰胺（DSA）和氯噻嗪（CT）的分离和定量。使用YMCTriart-苯基分析柱通过梯度洗脱成功分离，流动相为0.1%甲酸与乙醇，流速为1.0 mL/min，并在254.0 nm处进行光电二极管阵列检测。HCT和CAR在0.1至100.0 µg/mL的浓度范围内呈线性，DSA和CT在0.05至10.0 µg/mL的浓度范围内呈线性。所建议的色谱方法可以估计不同实际样品中的HCT和CAR。此外，它有助于同时监测它们的溶出曲线。所研究方法的性能按照国际协调会议（ICH）制定的指南进行了验证。此外，通过各种绿色度、蓝色度和白色度评估工具进一步确认了其生态可持续性以及适用性，并与官方和其他报道的程序进行了比较。此外，最近引入的碳足迹减少指数工具已用于评估所建议的方法，重点是估计碳排放。总体而言，所建议的方法被证明对于进行原料药形式和商业可得制剂的质量控制检查是有效的。
