Marzouk Hoda M, El-Hanboushy Sara, Obaydo Reem H, Fayez Yasmin M, Abdelkawy Mohamed, Lotfy Hayam M
Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt.
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Future University in Egypt, Cairo, 12311, Egypt.
BMC Chem. 2023 Aug 19;17(1):101. doi: 10.1186/s13065-023-01015-z.
Cardiovascular disorders are among the leading causes of death worldwide, especially hypertension, a silent killer syndrome requiring multiple drug therapy for appropriate management. Hydrochlorothiazide is an extensively utilized thiazide diuretic that combines with several antihypertensive drugs for effective treatment of hypertension. In this study, sustainable, innovative and accurate high performance liquid chromatographic methods with diode array and tandem mass detectors (HPLC-DAD and LC-MS/MS) were developed, optimized and validated for the concurrent determination of Hydrochlorothiazide (HCT) along with five antihypertensive drugs, namely; Valsartan (VAL), Amlodipine besylate (AML), Atenolol (ATN), Amiloride hydrochloride (AMI), and Candesartan cilextil (CAN) in their diverse pharmaceutical dosage forms and in the presence of Chlorothiazide (CT) and Salamide (DSA) as HCT officially identified impurities. The HPLC-DAD separation was achieved utilizing Inertsil ODS-3 C column (250 × 4.6 mm, 5 μm) attached with photodiode array detection at 225.0 nm. Gradient elution was performed utilizing a mixture of solvent A (20.0 mM potassium dihydrogen phosphate, pH 3.0 ± 0.2, adjusted with phosphoric acid) and solvent B (acetonitrile) at ambient temperature. Linearity ranges were 0.1-100.0 µg/mL for HCT, VAL, AML and CAN, 0.05 -100.0 µg/mL for both ATN and AMI and 0.05-8.0 µg/mL for both CT and DSA. Additionally, this work describes the use of liquid chromatography-electrospray-tandem mass spectrometry for the accurate detection and quantification of the impurities; CT and DSA in the negative mode utilizing triple quadrupole mass spectrometry. The linearity ranges for those impurities were 1.0-200.0 ng/mL and 5.0-200.0 ng/mL for CT and DSA, respectively. Developed methods' validation was achieved in accordance with International Conference on Harmonization (ICH) guidelines. Upon applying liquid chromatographic techniques for the drug analysis, a green and sustainable assessment have to be handled due to the consumption of energy and many solvents. Through the use of the HEXAGON, Analytical Greenness (AGREE) and White Analytical Chemistry (WAC) tools, greenness and sustainability have been statistically assessed. The optimized HPLC-DAD and LC-MS/MS methods were fast, accurate, precise, and sensitive, and consequently could be applied for conventional analysis and quality control of the proposed drugs in their miscellaneous dosage forms for the purpose of reducing laboratory wastes, time of the analysis time, effort, and cost.
心血管疾病是全球主要死因之一，尤其是高血压，这是一种需要多种药物治疗才能妥善管理的隐性杀手综合征。氢氯噻嗪是一种广泛使用的噻嗪类利尿剂，它与多种抗高血压药物联合使用，可有效治疗高血压。在本研究中，开发、优化并验证了采用二极管阵列和串联质谱检测器的可持续、创新且准确的高效液相色谱法（HPLC-DAD和LC-MS/MS），用于同时测定氢氯噻嗪（HCT）以及五种抗高血压药物，即缬沙坦（VAL）、苯磺酸氨氯地平（AML）、阿替洛尔（ATN）、盐酸阿米洛利（AMI）和坎地沙坦酯（CAN），这些药物存在于多种剂型中，且存在作为HCT官方认定杂质的氯噻嗪（CT）和沙拉米特（DSA）。HPLC-DAD分离采用Inertsil ODS-3 C柱（250×4.6 mm，5μm），在225.0 nm处进行光电二极管阵列检测。在室温下，使用溶剂A（20.0 mM磷酸二氢钾，pH 3.0±0.2，用磷酸调节）和溶剂B（乙腈）的混合物进行梯度洗脱。HCT、VAL、AML和CAN的线性范围为0.1 - 100.0μg/mL，ATN和AMI的线性范围为0.05 - 100.0μg/mL，CT和DSA的线性范围为0.05 - 8.0μg/mL。此外，这项工作描述了使用液相色谱 - 电喷雾 - 串联质谱法在负离子模式下利用三重四极杆质谱准确检测和定量杂质CT和DSA。这些杂质的线性范围分别为CT 1.0 - 200.0 ng/mL和DSA 5.0 - 200.0 ng/mL。所开发方法的验证符合国际协调会议（ICH）指南。在应用液相色谱技术进行药物分析时，由于能源和许多溶剂的消耗，必须进行绿色和可持续性评估。通过使用HEXAGON、分析绿色度（AGREE）和白色分析化学（WAC）工具，对绿色度和可持续性进行了统计评估。优化后的HPLC-DAD和LC-MS/MS方法快速、准确、精密且灵敏，因此可用于所提议药物多种剂型的常规分析和质量控制，以减少实验室废物、分析时间、工作量和成本。
