Résumé
@#To identify the related substances of cyclosporin A by LC-MS techniques, the separation of cyclosporin A and its related substances was carried out on a Hypersil BDS C18(100 mm×4. 6 mm, 2. 4 μm)column with isocratic elution by a mixture of acetonitrile-water-MTBE and formic acid(430 ∶520 ∶50 ∶1)as the mobile phase. Cyclosporin A and its 29 related substances(9 process related and 20 degradants)were well separated under the established conditions. Among them, 13 were listed in EP and the rest 16 were unknown products having not been reported before. Electrospray positive ionization high resolution TOF/MS was used for the determination of the accurate mass and elemental composition of parent ions of all the components, and triple quadrupoles tandem mass was employed for the product mass spectra determination. Thence, the structures of all the 29 detected substances were successfully characterized through spectra elucidation and the fragmentation pathways analysis. The established LC-MS method was successfully employed for the separation and identification of the related substances of cyclosporin A and it is useful for its fermentation processes and quality control.
Résumé
To identify the related substances of fusidic acid by LC-MS,separation was performed on an Agilent Extend-C18column(150 mm ×4. 6 mm,3. 5 μm)by linear gradient elution with a mobile phase consisting of methanol,acetonitrile and formic acid. Electrospray positive ionization high resolution TOF/MS was used for the determination of the accurate mass and elemental composition of parent ions of the related substances;triple qua-drupole tandem mass was employed for the mass spectra determination of the product. The structures of the related substances were then figured out through the elucidation of the fragment ions. Fusidic acid and its related sub-stances were adequately separated under the established HPLC conditions. Nineteen major related substances of fusidic acid were detected and speculated by hyphenated techniques. Eleven of them were recorded in European Pharmacopoeia,while the others have not been previously reported. The established LC-MS method is effective for the separation and identification of the related substances of fusidic acid and the results are useful for its storage conditions and quality assurance.
Résumé
Clinical symptoms with serum theoph ylline level above normal therapeutical range were analysed in 32 case. Methods: Theophylline 20μgmL-1 invserum was defined as the upper limit of normal therapeutical range. The case records with serum theo phylline concentraed ≥20μgmL-1 were selected from 324 cases, analyse d in combination with clinical symptoms. Results: Patients with serum theophylline concentration ≥20 μgmL-1 showed toxic reacti ons involving cardiovasucular, digestive, and nervous systems. One third of them took simultaneously other drugs which could decrease the metabolism of theophyl line. Conclusion: In order to prevent and diagnose toxicr eactions effectively, it's necessary to monitor the patients'serum theophylline level.