Zayed Sahar, Belal Fathalla
Unit of Drug Analysis, Faculty of Pharmacy, University of Mansoura, Mansoura, 35516, Egypt.
Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, University of Mansoura, Mansoura, 35516, Egypt.
Chem Cent J. 2017 May 4;11(1):36. doi: 10.1186/s13065-017-0264-6.
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. A combination of indacaterol maleate with glycopyrronium bromide has recently been approved as a once-daily maintenance therapy in patients with COPD. The very low dose (μg level/capsule) renders the analysis of such products challenges. This study reports for the first time about HPLC method for the quality control of such combination and it is a stability indicating at the same time.
A rapid, simple, precise and reproducible HPLC method was developed and validated for simultaneous determination of indacaterol maleate and glycopyrronium bromide using tenoxicam as an internal standard. The chromatographic separation was achieved on an onyx monolithic C18 column (100 × 4.6 mm) using a mobile phase consisting of acetonitrile and 30 mM phosphate buffer (pH 3.5) (30:70, v/v), run at a flow rate of 2 mL/min with UV detection at 210 nm. The total analysis time was less than 3 min. The HPLC method was validated for linearity, limits of detection and quantitation, precision, accuracy, system suitability and robustness. Calibration curves were obtained in the concentration ranges of 1-44 µg/mL for indacaterol maleate and 0.5-20 µg/mL for glycopyrronium bromide. Stability tests were done through exposure of the analyte solution for different stress conditions and the results indicate no interference of degradants with HPLC method.
The method was successfully applied for the quantitative analysis of indacaterol maleate and glycopyrronium bromide both individually and in a combined pharmaceutical inhaler capsules to support the quality control and to assure the therapeutic efficacy of the two drugs. The simple procedure involved in sample preparation and the short run-time added the important property of high throughput to the method. Graphical abstract Chemical structures and representative HPLC chromatogram of indacaterol maleate (IND; 22 μg/mL), glycopyrronium bromide (GLY; 10 μg/mL) and tenoxicam (IS, 15μg/mL) in commercial capsules.
慢性阻塞性肺疾病（COPD）是全球发病和死亡的主要原因。马来酸茚达特罗与格隆溴铵的联合用药最近已被批准作为COPD患者的每日一次维持治疗药物。极低剂量（微克水平/胶囊）使得对此类产品的分析具有挑战性。本研究首次报道了用于此类联合用药质量控制的高效液相色谱（HPLC）方法，并且该方法同时具有稳定性指示作用。
开发并验证了一种快速、简便、精确且可重现的HPLC方法，以替诺昔康为内标同时测定马来酸茚达特罗和格隆溴铵。在奥尼克斯整体式C18柱（100×4.6 mm）上进行色谱分离，流动相由乙腈和30 mM磷酸盐缓冲液（pH 3.5）（30:70，v/v）组成，流速为2 mL/min，在210 nm处进行紫外检测。总分析时间少于3分钟。对该HPLC方法的线性、检测限和定量限、精密度、准确度、系统适用性和稳健性进行了验证。马来酸茚达特罗的校准曲线在1 - 44 μg/mL浓度范围内获得，格隆溴铵的校准曲线在0.5 - 20 μg/mL浓度范围内获得。通过将分析物溶液暴露于不同的应激条件下进行稳定性试验，结果表明降解产物对HPLC方法无干扰。
该方法成功应用于马来酸茚达特罗和格隆溴铵的定量分析，无论是单独分析还是在复方吸入剂胶囊中分析，以支持质量控制并确保两种药物的治疗效果。样品制备过程简单且运行时间短，为该方法增添了高通量这一重要特性。图形摘要 市售胶囊中马来酸茚达特罗（IND；22 μg/mL）﹑格隆溴铵（GLY；10 μg/mL）和替诺昔康（内标，15 μg/mL）的化学结构及代表性HPLC色谱图
