Structural identification and characterization of potential impurities of pantoprazole sodium

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 45; no. 2; pp. 201 - 210
• Main Authors: MADHUSUDHAN REDDY, Ganta, VIJAYA BHASKAR, B, PRATAP REDDY, P, ASHOK, S, SUDHAKAR, P, MOSES BABU, J, VYAS, K, MUKKANTI, K
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Science 18.10.2007
• Subjects: 2-Pyridinylmethylsulfinylbenzimidazoles - analysis; 2-Pyridinylmethylsulfinylbenzimidazoles - chemistry; Analysis; Analytical, structural and metabolic biochemistry; Anti-Ulcer Agents - analysis; Anti-Ulcer Agents - chemistry; Biological and medical sciences; Chromatography, Liquid; Drug Contamination; Fundamental and applied biological sciences. Psychology; General pharmacology; Magnetic Resonance Spectroscopy; Mass Spectrometry; Medical sciences; Molecular Structure; Molecular Weight; Pharmacology. Drug treatments; Spectrophotometry, Infrared; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction; Impurity; H; Antiulcer agent; Identification; K; Proton pump inhibitor; Characterization; HRMS; Antisecretory agent; Qualitative analysis; Spectroscopy; Pantoprazole; Single crystal and XRD studies; Enzyme; Enzyme inhibitor; Liquid chromatography; X ray diffraction; Pantoprazole sodium; Single crystal; LC-MS; Sodium; Benzimidazole derivatives; exchanging ATPase; Hydrolases; Mass spectrometry; Structural analysis
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2007.05.032

Six impurities in pantoprazole sodium bulk drug substance were detected by a simple high performance liquid chromatographic method (HPLC) whose area percentage ranged from approximately 0.05 to 0.34%. Liquid chromatography-mass spectrometry (LC-MS) was performed to identify the molecular weight of the impurities. A thorough study was undertaken to characterize these impurities. These impurities were synthesized, subsequently characterized and were co-injected with the sample containing impurities and found the retention time match of the spiked impurities. Based on their spectral data (IR, NMR and MS), these impurities were characterized as; 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]thio]-1H-benzimidazole (Impurity-I); 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulfonyl]-1H-benzimidazole (Impurity-II); 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-1-oxide-2-pyridinyl)methyl]sulfonyl]-1H-benzimidazole (Impurity-III); 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]thio]-1-((3,4-dimethoxy-2-pyridinyl)methyl)-1H-benzimidazole (Impurity-IV); 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulfinyl]-1-((3,4-dimethoxy-2-pyridinyl)methyl)-1H-benzimidazole (Impurity-V); 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-1-oxide-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole (Impurity-VI). The formation of these impurities was proposed. The structure of the Impurity-II was unambiguously confirmed by single crystal X-ray diffraction (XRD) studies.