Hamdy Mohamed M A, Korany Mohamed A, Ebied Shaza A, Haggag Rim S
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt.
Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
J Chromatogr B Analyt Technol Biomed Life Sci. 2022 Mar 15;1193:123160. doi: 10.1016/j.jchromb.2022.123160. Epub 2022 Feb 15.
The binary mixtures of the novel oral anticoagulants (NOACs); Apixaban (APX), Edoxaban tosylate (EDX) and Rivaroxaban (RIV) with the lipid lowering statin; Rosuvastatin calcium were analyzed using a validated HPLC-DAD method. This method was suitable for the quantitative assay of the targeted mixtures in tablets and human plasma. The analysis in dosage form was a stability indicating one where the drugs were separated from possible degradation products arising from applying different stress conditions. For analysis in human plasma, EDX was used as internal standard in APX/ROS and RIV/ROS mixtures, while APX was used as internal standard in EDX/ROS mixture and the method was validated according to FDA regulation for analysis in biological fluids. A ZORBAX Eclipse column C18 (4.6 × 150 mm × 5 µm) was used as stationary phase with a gradient eluting mobile phase composed of acidified water and acetonitrile. The method selectivity was demonstrated by its ability to simultaneously analyze the drugs in presence of possible forced degradation products and dosage form excipients and in presence of plasma interferences (analysis in biological fluid) at a single wavelength (291 nm) with the use of the internal standard. The simplicity of the method emphasizes its capability to analyze the drugs in pharmaceutical preparations and human plasma. This is very important in regular clinical monitoring of the drugs plasma concentrations for cardiovascular patients medicated with either of these combinations, as prophylaxis from stroke, in order to prevent severe bleeding and to achieve optimum dose adjustment.
采用经过验证的高效液相色谱 - 二极管阵列检测法（HPLC - DAD）分析了新型口服抗凝剂（NOACs）阿哌沙班（APX）、甲苯磺酸依度沙班（EDX）和利伐沙班（RIV）与降脂他汀类药物瑞舒伐他汀钙的二元混合物。该方法适用于片剂和人血浆中目标混合物的定量测定。剂型分析是一种稳定性指示分析，其中药物与因施加不同应激条件而产生的可能降解产物分离。对于人血浆分析，在APX/ROS和RIV/ROS混合物中，EDX用作内标，而在EDX/ROS混合物中，APX用作内标，并且该方法根据FDA法规针对生物流体分析进行了验证。使用ZORBAX Eclipse C18柱（4.6×150 mm×5 µm）作为固定相，流动相采用由酸化水和乙腈组成的梯度洗脱。该方法的选择性通过其在使用内标的单一波长（291 nm）下，能够同时分析存在可能的强制降解产物和剂型辅料以及存在血浆干扰物（生物流体分析）时的药物来证明。该方法的简便性突出了其分析药物制剂和人血浆中药物的能力。这对于接受这些组合药物治疗的心血管疾病患者进行常规临床监测药物血浆浓度非常重要，作为预防中风的措施，以防止严重出血并实现最佳剂量调整。
