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.

中文翻译：

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LC-MS / MS用于Pan托拉唑原料中潜在遗传毒性杂质分析的开发和验证

top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）涉及六个潜在的遗传毒性杂质（PGI），后者是PPZS的起始原料。迄今为止，尚未开发出在毒理学关注水平阈值下进行PGI分离和定量的合适方法。在这项研究中，根据国际协调委员会（ICH）的指导原则，开发了一种灵敏可靠的液相色谱-串联质谱法，并已用于DMBZ中6种PGI的定量分析。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的范围内。回收率在94.32％–107.43％之间，RSD值低于6.5％。对DMBZ物质批次中的杂质进行定量分析表明，该方法在较低水平上具有很高的效率。因此，所提出的方法在DMBZ中PGI的检测和鉴定中是实用且有用的，并可用于确保在临床治疗中安全使用PPZS。