摘要
目的:建立以反相高效液相色谱法测定人尿中甲苯磺丁脲及其代谢产物羧基甲苯磺丁脲和羟基甲苯磺丁脲浓度的方法。方法:以氯磺丁脲为内标,尿样经酸化后用异丙醚萃取,并进样分析;色谱柱为DiamonsilTM C18,流动相为乙腈-0.05 mol.L-1NaH2PO4(pH4.0,梯度洗脱),流速为1.0 mL.min-1,检测波长为230 nm,柱温为40℃。结果:甲苯磺丁脲、羧基甲苯磺丁脲、羟基甲苯磺丁脲尿药浓度均在0.3～10μg.mL-1范围内线性关系良好(r分别为0.999 9、1.000 0、0.999 9),最低检测浓度均为0.1μg.mL-1。各样本低、中、高浓度的方法回收率在95.00%～105.88%之间,日内、日间RSD均<6%。结论:本方法简便、准确、灵敏、重复性好,适用于细胞色素P4502C9表型分析及甲苯磺丁脲与其代谢产物的人体药动学研究。
OBJECTIVE： To establish an RP-HPLC method for the concentration determination of tolbutamide and its metabolites carboxytolbutamide and hydroxytolbutamide in human urine. METHODS： The urine sample was acidified and extracted with isopropyl ether. The separation was carried out on DiamonsilTM C18（250 mm×4.6 mm, 5μm） column with mobile phase consisted of acetonitrile-0.05mol- L-1 NaH2PO4 （pH adjusted to 4.0, gradient elution） using chlorbutamide as internal standard. The flow rate was 1.0 mL-min-1 and the detection wavelength was 230 nm. The column temperature was 40 ~C. RESULTS： The linear ranges of tolbutamide, carboxytolbutamide and hydroxytolbutamide were 0.3 -10 μg. mL-1 （tolbutamide： r = 0.999 9; carboxytolbutamide： r= 1.000 0; hydroxytolbutamide：r=0.999 9）. The lowest detection concentrations were 0.1 μg. mL-1. The intra-day and inter-day RSD were all less than 6%. The low, middle and high extraction recoveries were between 95.00%～105.88%. CONCLUSION： The method is simple, accurate, sensitive and reproducible for the study of CYP2C9 phenotype analysis and the human pharmacokinetic study of tolbutamide and its metabolites.
出处
《中国药房》
CAS
CSCD
北大核心
2010年第46期4359-4361,共3页
China Pharmacy
