in vivo with high and long lasting antisecretory activity Wallmark et al 1985

In vivo with high and long lasting antisecretory

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in vivo with high and long lasting antisecretory activity (Wallmark et al. ,1985; Larsson et al. ,1983). Pantoprazole (PNT), 5-(difluo- romethoxy)-2-[[(3,4- dimethoxy-2-pyridinyl)methyl] sulfinyl]-1 H -benzimidazole is an oral pharmaceutically active compound having promising anti-ulcer activity (Kohl et al. , 1992) and belongs to the class of 2-[[(2- pyridyl) methyl]sulfinyl]-1 H -benzimidazoles. In general these classes of compounds were used for the prevention and treatment of gastric acid related diseases (Kohl et al. , 1988). Literature studies reveal different methods for the preparation of PNT (Kormer et al. , 1990). Numerous methods have been developed for the
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S. Pandey, P. Pandey, D. Mishra, U. K. Singh 176 determination of PNT in the bulk drug substance or dos- age forms, either alone or in the presence of other drugs. Techniques used for its assay include spectrophotometry (Moustafa et al. , 2000; Wahbi et al. , 2002; Rajic et al. , 2003; Salama et al. , 2003; Rahman et al. , 2005, 2006), polarography (Radi, 2003; Radi et al. , 2003), thermogra- vimetry (Reddy et al. , 2007), amperometry (Castro et al. , 2005), HPLC (Mansour et al. , 2000; Storms et al. , 2002; Sivkumar et al. , 2007, 2008; Margues et al. , 2007; Patel et al. , 2007; Zeinab et al. , 2006), GC method (Nanduri et al ., 2008), TLC (Agbaba et al. , 2004; Gosavi et al. 2006), and capillary electrophoresis (Tivesten et al. , 1999). The presence of impurities in an active pharmaceuti- cal ingredient (API) can have a significant impact on the quality and safety of the drug products. The regulatory framework basically addresses the development of analyti- cal approaches focused on the impurities contained in the drugs. The requirements for testing the impurities become increasingly more complex due to the fact that the sources of potential impurities are numerous, including diverse synthetic routes, possible side reactions, degradation re- actions affected by different storage conditions, different package materials, etc. PNT is synthesized by condensation of 5-(difluoromethoxy)-2-mercapto-1 H -benzimidazole (I) and 2-(chloromethyl)-3,4-dimethoxypiridine hydro- chloride in the presence of an inorganic base, to yield 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl) methyl] thio-1 H -benzimidazole (II), which—upon further oxidation with a suitable oxidizing agent eventually leads to pantoprazole. The route of synthesis and Chemical structures of the possible impurities contained in PNT are shown in Figure 1. The most important and critical step is PNT oxidation. Consequently, as a potential byproduct the sulfone, i.e., 5-(difluoromethoxy)-2-[[(3,4-dimethoxy- 2-pyridinyl) methyl] sulfonyl-1 H -benzimidazole (III), could appear via a structurally labile overoxidated sulf- oxide (Mathad et al. , 2004). Forced degradation studies of new drug substances and drug products are essential to help develop and demon- strate specificity of stability-indicating methods and to de - termine the degradation pathways and degradation products of the active ingredients. Procedures for the preparation of specific degradation products needed for method validation often emerge from these studies (Dan et al ., 2002).
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  • Summer '20
  • JESUS BAR
  • Chromatography, pH, High performance liquid chromatography, pnt

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