摘要
目的:建立固相萃取高效液相色谱测定生物样品中的甲苯磺丁脲和代谢产物浓度的方法,并用于研究甲苯磺丁脲人体代谢过程。方法:固相萃取净化和富集样品,建立高效液相色谱法测定人血清和尿中甲苯磺丁脲和代谢产物的浓度。色谱条件:色谱柱为Waters Spherisorb Phenyl色谱柱(4.6mm×250mm,5μm),流动相为甲醇-0.02mmol·L^(-1)pH 3.3乙酸钠缓冲液(28:72),流速1mL·min^(-1),检测波长:230nm。用该方法测定10名健康志愿者单次口服500mg血清和尿液中药物及其代谢产物浓度,应用3P97计算其的药动学参数。结果:血浆中甲苯磺丁脲线性范围为2-100μmol·L^(-1)(r=0.999),回收率为105.1%-103.9%。尿液中羧基甲苯磺丁脲、4-羟基甲苯磺丁脲和甲苯磺丁脲的线性范围为2-50μmol·L^(-1)(r=0.999)、1-50μmol·L^(-1)(r=0.999)和1-50μmol·L^(-1)(r=0.999),回收率为98.8%-100.1%,95.4%-103.5%和97.7%-106.6%。各样品的日内、日间精密度均≤15%。10名健康志愿者单次口服500mg甲苯磺丁脲的AuC_(0-∞)为(2644.6±472.8)μmol·L^(-1)·h,T_(max)为(1.4±0.6)h,C_(max)为(235.8±47.3)μmol·L^(-1),T_(1/2)为(6.9±2.1)h,MR_(0-24)为277.5±125.6。主要以羧基甲苯磺丁脲和4-羟基甲苯磺丁脲的形式经尿液排出。结论:方法灵敏、准确,重复性好,可用于甲苯磺丁脲的体内代谢过程研究。
Objective: To establish an HPLC method by solid-phase extraction in order to determine tolbutamide and its metabolites in human plasma and urine, and to study on its pharmacokinetics. Methods: The tolbutamide and its metabolites concentrations in human plasma and urine by solid-phase extraction were determined by HPLC. The Waters Spherisorb Phenyl column(4. 6mm×250mm, 5μm) was used as analytical column with a mobile phase consisted of methanol-0. 02mmol·L^(-1) pH3. 3 NaAc buffer(28:72). The flow rate was 1mL?min^(-1) with UV detection set at 230nm. The concentrations of tolbutamide and its metabolites in plasma and urine in healthy volunteers were determined by HPLC and the pharmacokinetic parameters were analyzed by 3P97. Results:The linear range was 2-100μmol·L(r=0. 999) for tolbutamide in human plasma utilizing solid phase extraction. The recovery was 105. 1%-103.9%. The linear range was 2-50μmol·L^(-1)(r=0.999) for carboxytolbutamide in human urine. The recovery was 98. 8%-100. 1%. The linear range was 1-50μmol·L^(-1)(r=0. 999)for 4-hydroxytolbutamide in human urine. The recovery was 95. 4%-103. 5%. The linear range was 1-50μmol·L ^(-1)(r=0. 999)for tolbutamide in human urine. The recovery was 97. 7%-106. 6%. The within-day and between -day deviations of all samples were less than 15%. After a single oral dose of 500mg tolbutamide, the main pharmacokinetic parameters AUC_(0-∞), T_(1-2), T_(max), C_(max) MR_(0-24) were(2644. 6±472. 8)μmol·L^(-1)?h,(6. 9±2. 1)h,(1. 4±0. 6)h,(235.8 ±47. 3)μmol·L^(-1) and 277. 5±125. 6. Conclusion:The method is simple and can be used to determined tolbutamide and its metabolites in biological samples. Tolbutamide was mainly excreted through urine in form of carboxytolbutamide and hydroxytolbutamide.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2005年第1期50-54,共5页
Chinese Journal of Pharmaceutical Analysis
基金
国家863计划支持项目
课题编号:2002AA2Z341L
