Spiridon A M, Neamtu J, Belu I, Turcu-Stiolica T S, Croitoru O
University of Medicine and Pharmacy of Craiova, Faculty of Pharmacy, Doctoral School.
Curr Health Sci J. 2015 Apr-Jun;41(2):172-178. doi: 10.12865/CHSJ.41.02.13. Epub 2015 Apr 10.
The concept of multidrug therapy with clopidogrel, acetylsalicylic acid and atorvastatin provides major advances for patients with acute coronary syndromes (ACS) treated invasively and conservatively to reduce the risk of ischemic events and improve survival. Dual antiplatelet therapy (DAPT) with acetylsalicylic acid and clopidogrel is currently the treatment of choice in acute coronary syndromes and prevention of thrombosis after coronary stent implementation. Present paper presents a simple, rapid and precise reversed phase high performance liquid chromatographic method for simultaneous estimation of clopidogrel hydrogen sulfate, acetylsalicylic acid and atorvastatin calcium from tablet dosage form. The cromatographic analysis was carried out using a ThermoFinnigan Chromatograph with UV detection and separation on an HDS Hypersil C18 column. The elution was isocratic with mobile phase consisting in mixture of 0.01M KH₂PO₄ buffer: acetonitrile: methanol. Chemicals were represented by clopidogrel bisulfat, atorvastatin calcium and acetylsalicylic acid standards with high purity. The quality control samples used in the accuracy and precision evaluation were spiked at low, medium and high concentration levels. Preliminary tests were performed to select optimum conditions for simultaneous separation of all three analytes such as mobile phase composition, proportion and pH. A satisfactory separation of all three drugs was achieved with a mobile phase of 0.01 M KH₂PO₄ buffer (pH adjusted to 2.6 with phosphoric acid):acetonitrile:methanol 20:40:40 v/v/v at flow rate of 0.8 ml/min. The proposed method was validated for linearity, precision and accuracy. The validated method can be successfully applied for simultaneous quantification of clopidogrel, acetylsalycilic acid and atorvastatin either in combination or in single dosage form in quality control analysis. The analytical conditions can also be performed for human plasma analysis.
氯吡格雷、乙酰水杨酸和阿托伐他汀联合用药的理念为接受侵入性和保守治疗的急性冠状动脉综合征（ACS）患者带来了重大进展，可降低缺血事件风险并提高生存率。乙酰水杨酸和氯吡格雷的双联抗血小板治疗（DAPT）是目前急性冠状动脉综合征以及冠状动脉支架植入术后预防血栓形成的首选治疗方法。本文介绍了一种简单、快速且精确的反相高效液相色谱法，用于同时测定片剂剂型中的硫酸氢氯吡格雷、乙酰水杨酸和阿托伐他汀钙。色谱分析使用配备紫外检测的ThermoFinnigan色谱仪，并在HDS Hypersil C18柱上进行分离。洗脱采用等度洗脱，流动相由0.01M KH₂PO₄缓冲液、乙腈和甲醇的混合物组成。化学对照品采用高纯度的硫酸氢氯吡格雷、阿托伐他汀钙和乙酰水杨酸标准品。在准确性和精密度评估中使用的质量控制样品添加了低、中、高浓度水平的药物。进行了初步试验以选择同时分离所有三种分析物的最佳条件，如流动相组成、比例和pH值。使用0.01M KH₂PO₄缓冲液（用磷酸调节pH至2.6）：乙腈：甲醇20:40:40 v/v/v的流动相，流速为0.8 ml/min，实现了所有三种药物的满意分离。该方法经过线性、精密度和准确性验证。验证后的方法可成功应用于质量控制分析中同时定量氯吡格雷、乙酰水杨酸和阿托伐他汀，无论是联合剂型还是单一剂型。该分析条件也可用于人体血浆分析。
