Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, P.O. Box 80260, Jeddah 21589, Saudi Arabia.
Department of Analytical Chemistry, Faculty of Pharmacy, Zagazig University, 44519 Zagazig, Egypt.
Molecules. 2019 Feb 27;24(5):843. doi: 10.3390/molecules24050843.
A high-performance liquid chromatography-diode array-mass spectrometric (LC-DAD-MS) method was developed and validated to investigate the related substances of olaparib (OLA) in bulk form. OLA was exposed to acid⁻base hydrolysis, boiling, oxidation with hydrogen peroxide, and UV light followed by LC-DAD-MS analysis. OLA and OLA-related substances were simultaneously and quantitatively monitored by DAD at 278 nm and triple quadrupole mass spectrometry (QQQ-MS). The investigated compounds were auto-scanned by an ion trap MS which applied positive and negative modes separately. The fragmentation pathway was confirmed by applying multi-steps fragmentation to identify the resulted cleaved ions and their parent ion. OLA was found to be sensitive to the alkaline hydrolysis and less sensitive to UV light. Two major hydrolytic degradation products, including the protonated molar ions / 299 and / 367, were identified. Three potential impurities were also characterized. The LC-MS limit of detection (LOD) and limit of quantification (LOQ) were 0.01 and 0.05 ng/µL, respectively. The quantitative results obtained by LC-DAD was comparable with that of LC-QQQ-MS. The proposed method shows good intra-day and inter-day precision with relative standard deviation (RSD) <2%.
建立并验证了高效液相色谱-二极管阵列-质谱法（LC-DAD-MS），用于研究奥拉帕利（OLA）原料药中的有关物质。将 OLA 分别进行酸堿水解、煮沸、过氧化氢氧化和紫外光照处理，然后进行 LC-DAD-MS 分析。通过 DAD 在 278nm 处同时和定量监测 OLA 和 OLA 相关物质，三重四极杆质谱（QQQ-MS）。通过离子阱 MS 对所研究的化合物进行自动扫描，分别采用正、负离子模式。通过多步裂解对得到的裂解离子及其母离子进行确认，从而确定了裂解途径。结果表明，OLA 对堿性水解敏感，对紫外光不敏感。鉴定出两种主要的水解降解产物，包括质子化的摩尔离子/299 和/367。还对三种潜在杂质进行了表征。LC-MS 的检测限（LOD）和定量限（LOQ）分别为 0.01 和 0.05ng/μL。LC-DAD 得到的定量结果与 LC-QQQ-MS 相当。该方法日内和日间精密度良好，相对标准偏差（RSD）<2%。
