Structural identification and characterization of potential impurities of pantoprazole sodium.
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.
Reddy
Ganta Madhusudhan
GM
Research and Development, Active Pharmaceutical Ingredients-IV, Dr. Reddy's Laboratories Ltd., IDA Jeedimetla, Hyderabad 500055, A.P., India.
Bhaskar
B Vijaya
BV
Reddy
P Pratap
PP
Ashok
S
S
Sudhakar
P
P
Babu
J Moses
JM
Vyas
K
K
Mukkanti
K
K
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000032:analysis* / Q000737:chemistry; D000897:Anti-Ulcer Agents / Q000032:analysis* / Q000737:chemistry; D002853:Chromatography, Liquid; D004340:Drug Contamination; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D008970:Molecular Weight; D000077402:Pantoprazole; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D000077402:Pantoprazole