Jeelani Salika, Kouznetsova Natalia
Analytical Development Laboratory, United States Pharmacopeial Convention (USP), Rockville, MD, 20852, USA.
Heliyon. 2023 Sep 9;9(9):e19993. doi: 10.1016/j.heliyon.2023.e19993. eCollection 2023 Sep.
A new fast stability-indication high performance liquid chromatography method was developed and validated for the determination of amlodipine besylate and its organic impurities in drug substance. The separation of amlodipine and its seven impurities was achieved on a core shell C18 column, 100 mm × 4.6 mm; 2.6 μm, within 15 min. The mobile phase comprised of 0.4% ammonium hydroxide in water and methanol delivered in a gradient mode; the method detection wavelength is 237 nm. The selected column is stable at high pH and provided a good peak shape for basic compounds. Amlodipine besylate was subject to acid, base, oxidative, thermal, and photolytic stress conditions. The degradation products were well resolved from the amlodipine peak and its impurities. Major degradants were analyzed by liquid chromatography coupled with single-quadrupole mass detector. Amlodipine peak was shown to be free of co-elution by mass spectral analysis in all stress conditions. The method was validated in terms of specificity, linearity, accuracy, precision, and robustness. The developed method could be applied for routine quality control analysis of amlodipine besylate drug substance.
开发并验证了一种新的快速稳定性指示高效液相色谱法，用于测定原料药中苯磺酸氨氯地平及其有机杂质。在100 mm×4.6 mm；2.6μm的核壳C18柱上，15分钟内实现了氨氯地平及其七种杂质的分离。流动相由水中0.4%氢氧化铵和甲醇以梯度模式输送组成；方法检测波长为237 nm。所选色谱柱在高pH值下稳定，为碱性化合物提供了良好的峰形。对苯磺酸氨氯地平进行了酸、碱、氧化、热和光解应激条件试验。降解产物与氨氯地平峰及其杂质得到了很好的分离。主要降解产物通过液相色谱-单四极杆质谱检测器进行分析。在所有应激条件下，通过质谱分析表明氨氯地平峰无共洗脱现象。该方法在特异性、线性、准确性、精密度和稳健性方面进行了验证。所开发的方法可用于苯磺酸氨氯地平原料药的常规质量控制分析。
