摘要
目的:建立灵敏专一的分析方法,测定人尿样中的罗红霉素(E-Rox)及其活性代谢产物Z-Rox。方法:采用高效液相色谱-电化学检测法(HPLC-ECD)与高效液相色谱-质谱法(HPLC-MS),样品经液-液萃取后,通过HPLC-ECD定量分析E-Rox浓度;然后,采用HPLC-MS,通过选择性离子反应监测方式(SRM),测定Z-Rox与E-Rox的尿药浓度比值,SRM扫描方式进行定量分析的碎片离子为m/z679(母离子m/z837)。结果:E-Rox和Z-Rox的线性范围分别为0.1~10mg·L-1和0.05~5mg·L-1,最低检测限分别为0.1mg·L-1和0.05mg·L-1,日内、日间RSD均小于12.5%。两法联用,分析了4名健康受试者单剂量口服150mgE-Rox后的尿样。结论:为深入研究E-Rox在人体内的代谢规律提供了可靠的分析方法,首次测定了人尿样中的活性代谢产物Z-Rox。
OBJECTIVE:To establish a sensitive method for the determination of roxithromycin (E Rox) and its active metabolite,(9Z) epimeric isomer (Z Rox).METHOD:E Rox and Z Rox were determined by using HPLC ECD in combination with HPLC MS.Quantitative analyse of E Rox was performed with HPLC ECD after liquid liquid extraction.Afterwards,the isomeric ratios of Z Rox and E Rox were determined by using HPLC MS in the selected reaction monitoring (SRM) mode via electrospray ionization (ESI).The SRM transition m/z 837 to m/z 679 was monitored for detection of Z Rox and E Rox isomers.RESULT:The calibration curves were over the concentration range of 0.1~10mg·L -1 for E Rox and 0.05~5mg·L -1 for Z Rox.The limits of quantification were found to be 0.1mg·L -1 for E Rox and 0.05mg·L -1 for Z Rox.The intra and inter day RSD were within 12.5% for each of analytes.The combined method was applied to the human urine samples from 4 healthy volunteers after oral administration of 150 mg E Rox.CONCLUSION:The combined method proved to be suitable for studies on the metabolism of E Rox in human.With the method,the concentrations of the active metabolite Z Rox in human urine were for the first time investigated.
出处
《中国药学杂志》
EI
CAS
CSCD
北大核心
1999年第5期318-321,共4页
Chinese Pharmaceutical Journal
关键词
尿样
罗红霉素
异构体
HPLC-ECD
HPLC-MS
roxithromycin,isomer,liquid chromatography mass spectrometry,electrochemical detection,metabolite