The current work describes the development and validation of a stability-indicating UPLC method for the determination of olmesaratan medoxomil (OLM), amlodipine besylate (AMB), hydrochlorothiazide (HCT) and their degradation products in the triple-combination tablet dosage form. The separation was achieved using a Zorbax Eclipse plus C₈ RRHD (100 mm × 3.0 mm), 1.8 μm column with gradient elution of mobile phase A containing 0.02 m of sodium phosphate buffer (pH 3.35) and mobile phase B as acetonitrile and water (90:10, v/v). The detector signal was monitored at UV 250 nm. Analytical performance of the optimized UPLC method was validated as per International Conference on Harmonization guidelines. The linearity ranges for OLM, AMB and HCT were 0.59–240, 0.30–60 and 0.37–150 μg/ml, respectively, with correlation coefficients >0.999. The dosage form was subjected to forced-degradation conditions of neutral, acidic and alkaline hydrolysis, oxidation and thermal and photodegradation. The method was proved to be stability indicating by demonstrating the specificity of the drugs from degradation products. The robustness of the method was evaluated through a two-level, three-factorial design with a multivariate approach. Statistical data analysis with best model fit P-value < 0.05 from an ANOVA test indicated that the influence of individual factors is relatively higher than the interaction effects. The method is useful for the analysis of drug products.

中文翻译：

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使用析因设计实验开发和验证用于测定奥美沙坦酯、氨氯地平和氢氯噻嗪三联剂型中降解杂质的稳定性指示 UPLC 方法

目前的工作描述了用于测定奥美沙坦酯 (OLM)、苯磺酸氨氯地平 (AMB)、氢氯噻嗪 (HCT) 及其在三联片剂型中的降解产物的稳定性指示 UPLC 方法的开发和验证。使用 Zorbax Eclipse plus C ₈ RRHD (100 mm × 3.0 mm)、1.8 μm 色谱柱实现分离，流动相 A 梯度洗脱，含 0.02  m磷酸钠缓冲液 (pH 3.35) 和流动相 B 作为乙腈和水 (90:10, v/v)。在 UV 250 nm 处监测检测器信号。优化的 UPLC 方法的分析性能已根据国际协调会议指南进行了验证。OLM、AMB 和 HCT 的线性范围分别为 0.59-240、0.30-60 和 0.37-150 μg/ml，相关系数 >0.999。该剂型经受中性、酸性和碱性水解、氧化以及热和光降解的强制降解条件。通过证明降解产物中药物的特异性，证明了该方法的稳定性。该方法的稳健性通过采用多变量方法的两水平三因素设计进行评估。具有最佳模型拟合的统计数据分析ANOVA 检验的P值 < 0.05 表明个体因素的影响相对高于交互影响。该方法可用于药物产品的分析。