ABSTRACT
OBJECTIVE： To establish a method for simultaneous determination of impurity E， impurity Ⅰ and impurity Ⅳ in crude drug and preparation of esomeprazole sodium. METHODS： LC-MS/MS method was adopted. The separation was performed on Agela VenusiL MP C18 column with mobile phase consisted of acetonitrile-water （gradient elution） at the flow rate of 0.2 mL/min. The column temperature was 35 ℃， and the sample size was 1 μL； analytes were analyzed by electro-spray ionization （ESI） in the multiple reaction monitoring mode， negative ion. The precursors of production transitions m/z 360.1→194.0 （impurity E）， m/z 375.8→210.7 （impurity Ⅰ）， m/z 330.2→312.1 （impurity Ⅳ） were used to measure impurity. RESULTS： The linear range of impurity E， impurity Ⅰ and impurity Ⅳ were 0.001 26-0.044 80 μg/mL （r＝0.994 7）， 0.001 34-0.045 2 μg/mL （r＝0.992 8） and 0.018 9-1.260 00 μg/mL （r＝0.991 4）. The limit of quantitation were 0.001 26， 0.001 34， 0.018 9 μg/mL； the detection limits were 0.000 41， 0.000 44， 0.006 3 μg/mL. RSDs of precision and reproducibility tests were all lower than 4％； RSDs of stability tests of impurity E and impurity Ⅰ were all lower than 10％（n＝5）， and that of impurity Ⅳ was higher than 15％ （n＝7）. The average recoveries were 87.69％-100.72％ （RSD＝4.29％， n＝9）， 90.04％-100.63％（RSD＝3.67％，n＝9）and 93.58％-101.86％（RSD＝2.66％，n＝9）. CONCLUSIONS： The method is accurate， rapid， sensitive， selective and suitable for the content determination of 3 impurities in crude drug and preparation of esomeprazole sodium.
ABSTRACT
OBJECTIVE: To establish the national reference standards of sulfadimidine impurities thus to provide guarantee for improving the standard of quality control of sulfadiazine in China. METHODS: First, the structures of sulfadimidine impurities A and E were validated by infrared spectrocopy, mass spectrum and nuclear magnetic resonance method. Then, the purities of impurities A and E were determined using the method of related substance test for sulphadiazine in the European Pharmacopoeia (version 9.0),their water content and residue on ignition were determined as well. The contents of sulfadimidine impurities A and E were determined by using mass balance method. Meanwhile, external standard method and nuclear magnetic quantitative method were used to calculate the content, which were mutually verified with the mass balance method. Finally, the correction factors of sulfadiazine impurities A and E at 241 nm were determined using standard curve method. RESULTS: The structures of sulfadimidine impurities A and E were confirmed, and the contents of impurities A and E were 99.1% and 98.7%, respectively, which were calculated by mass balance method. The results were consistent with those obtained from external standard method and nuclear magnetic quantification method. The correction factors of impurities A and E to sulfadimidine were 0.97 and 0.63, respectively. CONCLUSION: The first batch of national standard substances of sulfadimidine impurities A and E were established successfully.
ABSTRACT
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.
ABSTRACT
Related substances in pharmaceutical formulations are associated with their safety, efficacy and stability. However, there is no overall study already published on the assessment of related substances in the Compound Ketoconazole and Clobetasol Propionate Cream. In this work, a reliable HPLC-TOF-MS qua-litative method was developed for the analysis of related substances in this preparation with a quick and easy extraction procedure. Besides the active pharmaceutical ingredients, two compounds named ke-toconazole impurity B′ optical isomer and ketoconazole impurity E were identified. Furthermore, a new HPLC method for qualitative and quantitative assessment on related substances and degradation pro-ducts, which were found in the stability test, was established and validated. The single standard to determine multi-components method was applied in the quantitative analysis, which was an effective way for reducing cost and improving accuracy. This study can provide a creative idea for routine analysis of quality control of the Compound Ketoconazole and Clobetasol Propionate Cream.