Chen Yuyuan, Wu Song, Yang Qingyun
Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
J Anal Methods Chem. 2020 Mar 9;2020:6597363. doi: 10.1155/2020/6597363. eCollection 2020.
Pantoprazole sodium (PPZS) is a selective proton pump inhibitor used in the prevention and treatment of gastric acid-related diseases. Six potentially genotoxic impurities (PGIs) are involved in 5-difluoromethoxy-2-mercapto-1H-benzimidazole (DMBZ), which is the starting material of PPZS. To date, no suitable method has yet been developed for PGI separation and quantification at the threshold of toxicological concern levels. In this study, a sensitive and reliable liquid chromatography-tandem mass spectrometry method was developed and validated for the quantitative analysis of six PGIs in DMBZ according to the guidelines of the International Council for Harmonization (ICH). The calibration curves showed good linearity within the studied range, and the correlation coefficient of fitting exceeded 0.998 for each impurity. The sensitivity of the proposed method was in the range of 0.6-10.0 ng/mL. Good recoveries were observed in the range of 94.32%-107.43% with RSD values below 6.5%. Quantitative analysis of impurities in substance batches of DMBZ showed the high efficiency of the developed method at a low level. Hence, the proposed method is practical and useful in the detection and qualification of PGIs in DMBZ and may be applied to ensure the safe use of PPZS in clinical treatment.
泮托拉唑钠（PPZS）是一种用于预防和治疗胃酸相关疾病的选择性质子泵抑制剂。5-二氟甲氧基-2-巯基-1H-苯并咪唑（DMBZ）是PPZS的起始原料，其中涉及六种潜在的基因毒性杂质（PGIs）。迄今为止，尚未开发出适用于在毒理学关注阈值水平下分离和定量PGIs的方法。在本研究中，根据国际协调理事会（ICH）的指导原则，开发并验证了一种灵敏可靠的液相色谱-串联质谱法，用于定量分析DMBZ中的六种PGIs。校准曲线在研究范围内显示出良好的线性，每种杂质的拟合相关系数均超过0.998。所提出方法的灵敏度在0.6-10.0 ng/mL范围内。回收率在94.32%-107.43%范围内，相对标准偏差值低于6.5%，结果良好。对DMBZ物质批次中的杂质进行定量分析表明，所开发的方法在低水平下具有高效性。因此，所提出的方法在检测和鉴定DMBZ中的PGIs方面具有实用性和有效性，可用于确保PPZS在临床治疗中的安全使用。
