Koppala Srinivasarao, Reddy V Ranga, Anireddy Jaya Shree
Analytical Research and Process Development, Integrated Product Development Operations, Dr. Reddy's Laboratories Ltd, Bachupalli, Qutubullapur, 500 072 Telangana, India Centre for Chemical Sciences and Technology, Institute of Science and Technology, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad- 500085, Telangana, India
Analytical Research and Process Development, Integrated Product Development Operations, Dr. Reddy's Laboratories Ltd, Bachupalli, Qutubullapur, 500 072 Telangana, India.
J Chromatogr Sci. 2016 May-Jun;54(5):765-75. doi: 10.1093/chromsci/bmw008. Epub 2016 Feb 8.
A novel, simple, sensitive, selective and reproducible stability-indicating high performance liquid chromatographic method was developed for the quantitative determination of degradation products and process-related impurities of ketoprofen (KET) and omeprazole (OMZ) in combined oral solid dosage form. Chromatographic separation was achieved on a Phenomenex Luna C18 (2) column (150 × 4.6 mm, 5 μm) under gradient elution by using a binary mixture of potassium dihydrogen phosphate buffer and acetonitrile at a flow rate of 0.8 mL/min. Chromatogram was monitored at 233 nm for KET impurities and at 305 nm for OMZ impurities using a dual wavelength UV detector. Resolution for KET and OMZ and 14 impurities was found to be >1.5 for any pair of components. Typical retention behaviors of impurities at various pH values were depicted graphically. To prove the stability-indicating power of the method, the drug product was subjected to hydrolytic, oxidative, photolytic, humidity and thermal stress conditions as per ICH. The developed method was validated according to the current ICH guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, ruggedness and robustness.
建立了一种新颖、简便、灵敏、选择性好且可重现的稳定性指示高效液相色谱法，用于定量测定复方口服固体制剂中酮洛芬（KET）和奥美拉唑（OMZ）的降解产物及工艺相关杂质。采用 Phenomenex Luna C18 (2) 柱（150 × 4.6 mm，5 μm），以磷酸二氢钾缓冲液和乙腈的二元混合物为流动相，在梯度洗脱条件下进行色谱分离，流速为 0.8 mL/min。使用双波长紫外检测器，在 233 nm 处监测 KET 杂质的色谱图，在 305 nm 处监测 OMZ 杂质的色谱图。发现 KET、OMZ 及其 14 种杂质中任意一对组分的分离度均大于 1.5。以图形方式描绘了杂质在不同 pH 值下的典型保留行为。为证明该方法的稳定性指示能力，按照 ICH 规定，对药品进行了水解、氧化、光解、湿度和热应力条件试验。根据现行 ICH 指南，对所建立的方法进行了特异性、检测限、定量限、线性、准确度、精密度、耐用性和稳健性等方面的验证。
