■普拉赛替尼,RET酶的靶向抑制剂,在以铂类为基础的化疗后出现RET基因融合突变为特征的局部晚期或转移性非小细胞肺癌(NSCLC)成年患者的治疗中发挥关键作用.然而,普雷替尼生产和降解产生的杂质有可能影响其治疗有效性和安全性.
■要解决此问题,建立了一种液相色谱方法,并对该方法进行了验证,以对普雷替尼及其相关杂质进行特异性鉴定.通过尺寸为4.6mm×250mm和粒径为5μm的WatersX桥C18柱实现了普雷替尼及其相关杂质的分离。流动相A由20mmol/L磷酸二氢钾(KH2PO4)和乙腈(ACN)以19:1的体积比组成,而流动相B仅由ACN组成,利用梯度洗脱技术。在260nm的波长下进行检测,注射体积为10μL,流速为1.0mL/min。
■本研究中建立的色谱方法根据ICHQ2(R1)指南进行了验证。该方法在特定浓度范围内表现出优异的线性(imp-A:0.035-10.21μg/mL;imp-B:0.09-10.16μg/mL;imp-C:0.15-10.19μg/mL;普雷替尼:0.04-10.32μg/mL)。此外,该方法具有较高的灵敏度,杂质A的检测限,B,C,和普雷替尼0.01、0.03、0.015和0.013μg/mL,分别,定量限为0.035、0.09、0.05和0.04μg/mL,分别。就特异性而言,稳定性,重复性,准确度,和鲁棒性,该方法符合验证验收标准。总的来说,本研究建立的色谱技术可以有效分离普雷替尼及其杂质,为杂质的准确检测和定量提供可靠的保证。
■本研究中开发的色谱方法可用于检测普雷替尼及其杂质,的质量研究提供了重要的参考。
UNASSIGNED: 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.
UNASSIGNED: 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 C18 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 (KH2PO4) 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.
UNASSIGNED: 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.
UNASSIGNED: 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.