Pantoprazole sodium, a substituted benzimidazole derivative, is an irreversible proton pump inhibitor which is primarily used for the treatment of duodenal ulcers, gastric ulcers, and gastroesophageal reflux disease (GERD). The monographs of European Pharmacopoeia (Ph. Eur.) and United States Pharmaco-poeia (USP) specify six impurities, viz.; impurities A, B, C, D, E and F, respectively for its active phar-maceutical ingredient (API). The identification and synthesis of all impurities except impurity E are well described in the literature; however, there is no report related to impurity E. The prospects to the for-mation and controlling of impurity E up to ≤0.03％ in the synthesis of pantoprazole sodium sesquihydrate (PAN) were discussed in detail for the first time. The present work described the journey towards the successful development of an optimal preparation procedure of dimer impurity E. The most plausible mechanism involved in the formation of impurity E has been proposed.

One unknown impurity(Imp-II)during the analysis of laboratory batches of isoproterenol hydrochloride was detected in the level ranging from 0.04% to 0.12% by high performance liquid chromatography with UV detection. The unknown impurity structure was proposed as 4-[2-(propan-2-ylamino)ethyl]benzene-1,2-diol (Imp-Ⅱ)using the liquid chromatography–mass spectrophotometry(LC–MS)analysis.Imp-Ⅱ was isolated by semi-preparative liquid chromatography from the impurity-enriched reaction crude sample. Its proposed structure was confirmed by nuclear magnetic spectroscopy such as 1H, 13C,DEPT(1D NMR),HSQC(2D NMR) and infrared spectroscopy(IR),and retention time and purity with HPLC followed by the chemical synthesis. Due to less removable nature of Imp-II during the purification,the synthetic process was optimized proficiently to control the formation of Imp-II below to the limit<0.12% in the course of reaction.The new chemical route was developed for the preparation of this impurity in required quantity with purity to use as reference standard. The most probable mechanism for the formation of Imp-II was discussed in details.