非布司他在健康受试者体内的尿药排泄特征

 目的 建立人尿样中非布司他浓度的液相色谱-质谱联用（LC-MS）测定法，并研究健康中国受试者口服非布司他片后非布司他的尿药排泄特征。方法 尿液样品酸化后用乙酸乙酯提取，进行LC-MS分析。色谱柱为Hedera ODS-2，流动相为甲醇-10 mmol·L-1的醋酸铵水溶液（含0.05%甲酸）(70∶30)。12 名健康受试者分别单次口服非布司他片80 mg（规格：80 mg）后，测定尿药浓度，计算尿药排泄参数，并进行统计分析。结果 12 名健康受试者口服80 mg非布司他后，48 h内的尿药累积排泄量为(2.684±0.838) mg，累积排泄率为(3.4±1.0)%。男性与女性受试者间的累积排泄量和最大排泄速率无显著性差异。结论 非布司他在健康中国受试者体内的尿药排泄参数与已有文献报道的结果基本一致，且不存在性别差异。

Study on Urinary Excretion Characteristics of Febuxostat in Healthy Chinese Volunteers

OBJECTIVE To develop an LC-MS method for the determination of febuxostat in human urine sample， and to investigate the urinary excretion characteristics of febuxostat in healthy Chinese volunteers. METHODS After acidification， the urine sample was extracted with ethyl acetate and separated on a Hanbon Hedera ODS-2- C₁₈ column， with a mobile phase of 10 mmol·L-1 ammonium acetate buffer solution containing 0.05% formic acid-methanol (30∶70). Twelve healthy volunteers were given single oral dose of 80 mg febuxostat. The concentrations of febuxostat in urine were determined， and the pharmacokinetic parameters of febuxostat were calculated and compared between male and female volunteers by statistical analysis. RESULTS The accumulated amount of febuxostat excreted in urine in 48 h was （2.684 ±0.838）mg. The accumulated excretion rate was (3.4 ± 1.0)%.The urinary excretion characteristics of febuxostat had no significant difference between the male and the female volunteers. CONCLUSION The urinary excretion characteristics of febuxostat in healthy Chinese volunteers is consistent with those reported in literature. There is no significant difference between the male and the female volunteers.