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目的:建立固相萃取高效液相色谱测定人血浆和尿液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 5 μm Phenyl色谱柱(4.6 mm×250 mm),流动相为甲醇-0.02 mmol·L-1pH 3.3乙酸钠缓冲液(28∶72),流速1 ml·min-1,检测波长:230 nm。用该方法测定10名健康志愿者单次口服500 mg甲苯磺丁脲后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％。健康志愿者单次口服500 mg甲苯磺丁脲的AUC0-∞为 2644.6 ±472.8 μmol·h-1·L-1,Tmax是1.4±0.6 h,Cmax是235.8±47.3 μmol·L-1,T1/2为6.9±2.1 h,MR0-24=277.5±125.6。结论:甲苯磺丁脲及其代谢产物的固相萃取高效液相色谱法灵敏、准确,重复性好,可用于甲苯磺丁
OBJECTIVE: To establish a method for the determination of tolbutamide and its metabolites in human plasma and urine by high performance liquid chromatography with solid-phase extraction and to study the metabolic process of tolbutamide in human. Methods: Purification and enrichment of samples by solid-phase extraction and establishment of high performance liquid chromatography for the determination of tolbutamide and its metabolites in human serum and urine. Chromatographic conditions: a Waters Spherisorb 5 μm Phenyl column (4.6 mm × 250 mm) with a mobile phase of methanol-0.02 mmol·L-1 pH 3.3 sodium acetate buffer (28:72) at a flow rate of 1 ml · min -1 , Detection wavelength: 230 nm. Using this method, the concentrations of drugs and their metabolites in serum and urine of 10 healthy volunteers after a single oral dose of 500 mg tolbutamide were determined and the pharmacokinetic parameters were calculated using 3p97. Results: The linear range of tolbutamide was 2 ~ 100μmol·L-1 (r = 0.999). The recoveries ranged from 105.1% to 103.9%. The linear range of urinary carboxytolbutamide, 4-hydroxytoluenebutamide and tolbutamide were 2 ~ 50μmol·L -1 (r = 0.999), 1 ~ 50μmol·L -1 (r = 0.999) and The recoveries ranged from 98.8% to 100.1%, from 95.4% to 103.5% and from 97.7% to 106.6%, respectively, with a range of 1 ~ 50μmol·L -1 (r = 0.999) The daily, intra-day precision of all samples were ≤15%. The AUC0-∞ of single oral dose of tolbutamide for healthy volunteers was 2644.6 ± 472.8 μmol · h-1 · L-1, the Tmax was 1.4 ± 0.6 h, the Cmax was 235.8 ± 47.3 μmol·L-1, the T1 / 2 6.9 ± 2.1 h, MR0-24 = 277.5 ± 125.6. Conclusion: Tolbutamide and its metabolites are sensitive, accurate and reproducible with high performance liquid chromatography