摘要
目的初步阐明葡磷酰胺在大鼠体内的代谢情况。方法大鼠静脉给予葡磷酰胺50mg·kg-1,采用液相色谱-质谱联用法对大鼠尿中的代谢产物进行分析。分别在正、负离子两种检测方式采用一级全扫描、产物离子扫描、中性丢失扫描、母离子扫描等多种扫描方式下对代谢物进行检测。结果在正离子检测方式下,除原形外共检测到两种代谢物,即异磷酰胺氮芥和异磷酰胺氮芥脱卤素后生成的单胺丙啶基衍生物;在负离子检测方式下,由于异磷酰胺氮芥等化合物无质谱响应而只检测到葡磷酰胺原形。稳定性实验证明在大鼠尿中所检测到的两种化合物为代谢产物而非降解产物。结论葡磷酰胺在大鼠尿样中主要以原形的形式存在,另外还检测到异磷酰胺氮芥和异磷酰胺氮芥的单胺丙啶基衍生物两种代谢产物。
Aim To elucidate the metabolic pathway of glufosfamide in rats. Methods In this study, a liquid chromatography-tandem mass spectrometric method was developed and applied to characterize the metabolites of glufosfamide in rat urine, after an iv administration of 50 mg· kg^-1. The analysis was performed under two ionization modes in two different chromatographic systems, separately. To make sure that the compounds detected in rat urine were metabolites or degradation products, the stability of glufosfamide, isophosphoramide mustard （ M1 ） , and the degradation products of M1 in urine were investigated. Results In positive ionization mode, besides glufosfamide, two metabolites, isophosphoramide mustard and monoaziridinyl derivative of isophosphoramide mustard, were detected. In negative ionization mode, only glufosfamide itself was detected, while derivatives of isophosphoramide mustard have no response in such condition. Conclusion Glufosfamide was mainly unchanged excreted in urine, and two metabolites were detected as isophosphoramide mustard and monoaziridinyl derivative of isophosphoramide mustard.
出处
《药学学报》
CAS
CSCD
北大核心
2006年第6期513-517,共5页
Acta Pharmaceutica Sinica
基金
国家高技术研究发展计划(863计划)资助项目(2005AA2Z3C70).
