Wang Jing, Zhu Yonghong, Qin Jisu, Wu Wenyi, Huang Rongrong, Cai Liangliang
Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong, China.
Department of Pharmacy, Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Nantong, China.
Front Chem. 2024 Nov 12;12:1487108. doi: 10.3389/fchem.2024.1487108. eCollection 2024.
Ponatinib, a third-generation tyrosine kinase inhibitor, is employed in the management of adult chronic myeloid leukemia. Nevertheless, the presence of process impurities and degradation impurities linked to ponatinib may potentially influence its effectiveness and safety. Therefore, the objective of this research was to establish a robust liquid chromatography method and systematically validate it for the detection of substances related to ponatinib.
The separation of ponatinib and its impurities was conducted using an Agilent 5HC-C chromatographic column (4.6 mm × 250 mm, 5 μm). The mobile phase A comprised a mixture of water and acetonitrile in a 9:1 ratio, with an aqueous solution of pH 2.4 containing 2 mM potassium dihydrogen phosphate and 0.4% triethylamine. Mobile phase B, consisting of acetonitrile, was eluted in a gradient fashion. The flow rate was set at 1.0 mL/min, detection wavelength at 250 nm, column temperature at 40°C, and injection volume at 10 μL.
The method demonstrated high specificity, sensitivity, solution stability, linearity, precision, accuracy, and robustness. Additionally, this research unveiled a novel compound, imp-B, generated via the oxidative degradation of ponatinib. The molecular structure of the newly discovered product was elucidated through the utilization of nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS).
In conclusion, the chromatographic method developed in this study has the potential to be utilized for the detection of ponatinib and its impurities, thereby offering significant insights for quality assessment in ponatinib research.
波纳替尼是一种第三代酪氨酸激酶抑制剂，用于治疗成人慢性髓性白血病。然而，与波纳替尼相关的工艺杂质和降解杂质的存在可能会影响其有效性和安全性。因此，本研究的目的是建立一种可靠的液相色谱方法，并对其进行系统验证，以检测与波纳替尼相关的物质。
使用安捷伦5HC-C色谱柱（4.6 mm×250 mm，5μm）分离波纳替尼及其杂质。流动相A由水和乙腈按9:1的比例混合而成，为pH 2.4的水溶液，含有2 mM磷酸二氢钾和0.4%三乙胺。流动相B由乙腈组成，采用梯度洗脱。流速设定为1.0 mL/min，检测波长为250 nm，柱温为40°C，进样量为10μL。
该方法具有高特异性、灵敏度、溶液稳定性、线性、精密度、准确度和稳健性。此外，本研究还发现了一种通过波纳替尼氧化降解产生的新化合物，即杂质B。通过核磁共振（NMR）和高分辨率质谱（HRMS）对新发现产物的分子结构进行了阐明。
总之，本研究开发的色谱方法有潜力用于检测波纳替尼及其杂质，从而为波纳替尼研究中的质量评估提供重要见解。
