Zhu Yonghong, Qin Jisu, Wu Wenyi, Cai Liangliang
Department of Pharmacy, Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Nantong, Jiangsu, China.
Department of Pharmacy, Affiliated Hospital of Nantong University, Pharmacy School of Nantong University, Nantong, China.
Front Chem. 2024 Aug 21;12:1450692. doi: 10.3389/fchem.2024.1450692. eCollection 2024.
Pralsetinib, a targeted inhibitor of the RET enzyme, plays a critical role in the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) characterized by RET gene fusion mutations following platinum-based chemotherapy. Nevertheless, impurities resulting from the manufacturing and degradation of pralsetinib have the potential to impact its therapeutic effectiveness and safety profile.
To address this issue, a liquid chromatography method was developed and validated for the specific identification of pralsetinib and its related impurities. The separation of pralsetinib and its related impurities was achieved via a Waters X Bridge C column with dimensions of 4.6 mm × 250 mm and a particle size of 5 μm. Mobile phase A was composed of 20 mmol/L potassium dihydrogen phosphate (KHPO4) and acetonitrile (ACN) at a volume ratio of 19:1, while mobile phase B consisted solely of ACN, utilizing a gradient elution technique. Detection was performed at a wavelength of 260 nm, with an injection volume of 10 μL and a flow rate of 1.0 mL/min.
The chromatographic method established in this study was validated according to the ICH Q2 (R1) guidelines. The method demonstrated excellent linearity over a specific concentration range (imp-A: 0.035-10.21 μg/mL; imp-B: 0.09-10.16 μg/mL; imp-C: 0.15-10.19 μg/mL; pralsetinib: 0.04-10.32 μg/mL). Additionally, the method possesses high sensitivity, with detection limits for impurities A, B, C, and pralsetinib of 0.01, 0.03, 0.015, and 0.013 μg/mL, respectively, and quantification limits of 0.035, 0.09, 0.05, and 0.04 μg/mL, respectively. In terms of specificity, stability, repeatability, accuracy, and robustness, the method met the validation acceptance criteria. Overall, the chromatographic technique established in this study can effectively separate pralsetinib and its impurities, providing reliable assurance for the accurate detection and quantification of impurities.
The chromatographic method developed in this study can be utilized for the detection of pralsetinib and its impurities, offering a crucial reference for research on the quality of pralsetinib.
普拉替尼是一种RET酶的靶向抑制剂，在治疗铂类化疗后出现RET基因融合突变的局部晚期或转移性非小细胞肺癌（NSCLC）成年患者中发挥着关键作用。然而，普拉替尼生产和降解产生的杂质有可能影响其治疗效果和安全性。
为解决这一问题，开发并验证了一种液相色谱法，用于特异性鉴定普拉替尼及其相关杂质。普拉替尼及其相关杂质的分离通过一根尺寸为4.6 mm×250 mm、粒径为5μm的沃特世X Bridge C柱实现。流动相A由20 mmol/L磷酸二氢钾（KHPO4）和乙腈（ACN）按体积比19:1组成，而流动相B仅由ACN组成，采用梯度洗脱技术。检测波长为260 nm，进样体积为10μL，流速为1.0 mL/min。
本研究建立的色谱方法根据ICH Q2（R1）指南进行了验证。该方法在特定浓度范围内表现出良好线性（杂质A：0.035 - 10.21μg/mL；杂质B：0.09 - 10.16μg/mL；杂质C：0.15 - 10.19μg/mL；普拉替尼：0.04 - 10.32μg/mL）。此外，该方法具有高灵敏度，杂质A、B、C和普拉替尼的检测限分别为0.01、0.03、0.015和0.013μg/mL，定量限分别为0.035、0.09、0.05和0.04μg/mL。在特异性、稳定性、重复性、准确性和稳健性方面，该方法符合验证验收标准。总体而言，本研究建立的色谱技术能够有效分离普拉替尼及其杂质，为杂质的准确检测和定量提供可靠保证。
本研究开发的色谱方法可用于检测普拉替尼及其杂质，为普拉替尼质量研究提供了重要参考。
