Development and Validation of LC-MS/MS for Analyzing Potential Genotoxic Impurities in Pantoprazole Starting Materials

摘要

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.