人尿中磺化脱氢松香酸和铋的测定及尿药排泄特征研究

 目的 分别建立测定人尿中磺化脱氢松香酸(Ecabet)的液质联用法和铋(Bi)的氢化原子荧光法，考察二者在中国健康受试者尿液中的排泄特征。方法 尿液样品以甲醇沉淀并以乙酸酸化后进行液相色谱-质谱联用（LC-MS）分析测定磺化脱氢松香酸，采用Hanbon ODS-2色谱柱，流动相为甲醇-20 mmol·L^-1醋酸铵水溶液(55∶45)，质谱采用电喷雾离子源四级杆质谱和负离子选择性离子检测；以氢化物-原子荧光光谱（HG-AFS）法测定尿样中铋，样品经硝酸和高氯酸湿法消化后稀释进样。10名受试者单次口服碱式依卡倍特铋干混悬剂800 mg，测定磺化脱氢松香酸和铋的尿药排泄参数。结果 磺化脱氢松香酸在20.44~30 660 ng·mL^-1内线性关系良好，平均回收率大于92.8%，铋在0.3~40 ng·mL^-1内线性关系良好，平均回收率大于92.0%。受试者服药后，磺化脱氢松香酸和铋在72 h后基本随尿排泄完全，受试者服药后0~2 h间，磺化脱氢松香酸和铋经尿排泄速率最大；平均累计排泄百分率分别为(0.9±0.6)%和(0.02±0.01)%。结论 这两种测定方法适用于人尿中磺化脱氢松香酸和铋的测定及其尿药排泄特征研究。

Determination of Ecabet and Bismuth in Human Urine and Study on Their Urinary Excretion Profiles

OBJECTIVE To establish an HPLC-MS method for the determination of ecabet and a HG-AFS method for the determination of bismuth,and to investigate their urinary excretion profiles after oral administration of ecabet bismuth suspension in healthy volunteers.METHODS Urine samples were precipitated,acidized,and separated on an Hanbon ODS-2 column with methanol-20 mmol·L-1 ammonium(55∶45) as a mobile phase.Electrospray ionization source and negative ion mode for MS were used.A sensitive hydride generation atomic fluorescence spectrophotometry(HG-AFS) method for the determination of bismuth was also developed and validated.Urine samples were digested using wet digestion method.Ten healthy volunteers were given single oral dose of 800 mg ecabet bismuth suspension.RESULTS The calibration curve in urine was linear in the range of 20.44-30 660 ng·mL-1 for ecabet and 0.3-40 ng·mL-1 for bismuth,respectively.The average recoveries were more than 92.8% and 92.0%,respectively.After the volunteers took the suspensions,the average urinary excretion rates of ecabet and bismuth were highest at 0-2 h and the average cumulative excretion percentages of ecabet and bismuth in urine within 72 h were(0.9±0.6)% and(0.02±0.01)%,respectively.CONCLUSION The methods are suitable for the determination of ecabet and bismuth in human urine and for the investigation on their urinary excretion profiles.