Salman D, Peron J-M R, Goronga T, Barton S, Swinden J, Nabhani-Gebara S
School of Life Sciences, Pharmacy and Chemistry, Faculty of Science, Engineering and Computing, Kingston University-London, Kingston upon Thames, London KT1 2EE, UK.
Ann Pharm Fr. 2016 Mar;74(2):119-28. doi: 10.1016/j.pharma.2015.09.004. Epub 2015 Nov 3.
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.
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.
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.
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.
本研究旨在对异环磷酰胺在多种应激条件下进行强制降解研究，以考察所建立的高效液相色谱（HPLC）方法的稳健性。同时，还旨在通过HPLC和核磁共振（NMR）进一步深入了解异环磷酰胺的稳定性及其降解情况。
将异环磷酰胺溶液（20mg/mL；n = 15，20mL）分别在加热（70°C）、酸性（pH 1和4）及碱性（pH 10和12）条件下进行一式三份的应激处理。定期使用HPLC和傅里叶变换核磁共振（FT-NMR）对样品进行分析。
异环磷酰胺在弱酸性条件（pH 4）下最稳定。NMR结果表明，异环磷酰胺的降解机制涉及磷氮键的断裂。对于所有应激条件，HPLC均无法检测到NMR所检测出的异环磷酰胺降解产物。
这些结果表明，所建立的异环磷酰胺HPLC方法未能检测出NMR显示的降解产物。可能是降解产物与异环磷酰胺共洗脱、未完全洗脱或不适用于所采用的检测方法。因此，研究异环磷酰胺的稳定性需要采用不存在上述缺点的其他技术。
