HPLC & NMR-based forced degradation studies of ifosfamide: The potential of NMR in stability studies.

PURPOSE: The aim of this study is to conduct a forced degradation study on ifosfamide under several stress conditions to investigate the robustness of the developed HPLC method. It also aims to provide further insight into the stability of ifosfamide and its degradation profile using both HPLC and NMR. METHODS: Ifosfamide solutions (20mg/mL; n=15, 20mL) were stressed in triplicate by heating (70°C), under acidic (pH 1 & 4) and alkaline (pH 10 & 12) conditions. Samples were analysed periodically using HPLC and FT-NMR. RESULTS AND DISCUSSION: Ifosfamide was most stable under weakly acidic conditions (pH 4). NMR results suggested that the mechanism of ifosfamide degradation involves the cleavage of the PN bond. For all stress conditions, HPLC was not able to detect ifosfamide degradation products that were detected by NMR. CONCLUSION: These results suggest that the developed HPLC method for ifosfamide did not detect the degradation products shown by NMR. It is possible that degradation products co-elute with ifosfamide, do not elute altogether or are not amenable to the detection method employed. Therefore, investigation of ifosfamide stability requires additional techniques that do not suffer from the aforementioned shortcomings.

Effects of test conditions on the susceptibility of staphylococci in vitro to cephradine, cephaloridine, cephalexin, and cefuroxime.

Methicillin-resistant staphylococci were tested for susceptibility to cephradine, cephaloridine, cephalexin, and cefuroxime and 30 degree C and 37 degree C on ordinary media and on media of enhanced osmotic strength. The coagulase-negative strains were divided into Staphylococcus epidermis and Staphylococcus hominis. Generally the number of susceptible strains decreased with low incubation temperature and osmotic support. When Staphylococcus aureus was tested against cephalexin and cefuroxime, most were susceptible at 37 degree C whereas all were resistant at 30 degree C. A similar trend was found in the case of cephradine, where it was accentuated by osmotic support. While almost all strains of Staph. epidermidis were sensitive to all four drugs under all test conditions, the susceptibility of Staph. hominis was generally decreased by either lower incubation temperature or osmotic support or both.

The aetiology and prevention of shunt nephritis.

The pathogenesis of shunt nephritis is reviewed and attention is drawn to the association between this disease and chronic shunt colonisation with delayed diagnosis. The results of applying a surveillance scheme, involving serological to patients having shunt surgery are reported. Ten cases of shunt nephritis occurred in a group of patients not followed by this method, whereas only one case occurred in the surveillance group.