天津医药

• 论著 •    

健康人口服复方二甲双胍格列吡嗪片尿药排泄研究

佟若菲   

  1. 天津市儿童医院
  • 收稿日期:2011-05-03 修回日期:2011-07-20 出版日期:2012-01-15 发布日期:2012-01-15
  • 通讯作者: 佟若菲

Analysis of excretions in urine of metformin-glipizide tablet after oral administration in healthy human

  • Received:2011-05-03 Revised:2011-07-20 Published:2012-01-15 Online:2012-01-15

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摘要： 建立二甲双胍和格列吡嗪尿药浓度的测定方法，研究健康人口服二甲双胍格列吡嗪片后二甲双胍和格列吡嗪的人体尿药排泄特征。方法：二甲双胍尿液样品用流动相稀释，经涡旋高速离心后，采用 Lichrospher ODS色谱柱分离，流动相为乙腈-3 mmoL?L-1十二烷基硫酸钠（含0.5% 三乙胺，用H3PO4 调PH至4.0）（25∶75），用紫外检测器检测，检测波长为232nm。格列吡嗪尿液样品经盐酸酸化后用乙酸乙酯提取，采用 Lichrospher ODS色谱柱分离，流动相为乙腈-0.1%的乙酸水溶液（含10 mmoL?L-1的醋酸铵）（55∶45），质谱采用电喷雾离子源和选择性离子检测方式。10名健康受试者单次口服二甲双胍格列吡嗪片两片（含500mg 盐酸二甲双胍/5mg 格列吡嗪）后，测定二甲双胍及格列吡嗪尿药浓度，评价其尿药排泄特征。结果：高、中、低浓度的日间与日内精密度均小于10%。10名健康受试者单次口服二甲双胍格列吡嗪片后，24 h内尿液中二甲双胍及格列吡嗪的累积排泄量分别为102.5 ± 27.3 mg、452.2 ± 191.4 μg，平均累积排泄率分别为26.27 % ± 7.0 %和9.04 % ± 3.83 %。结论：建立的人尿样中格列吡嗪的HPLC-MS测定方法和二甲双胍的HPLC测定方法准确、灵敏，适用于尿药排泄研究。

关键词: 二甲双胍, 格列吡嗪, LC-MS, HPLC, 尿药排泄

Abstract: ABSTRACT OBJECTIVE To develop methods for the determination of metformin and glipizide in human urine and to study the urinary excretions of drugs in healthy Chinese volunteers after single dose administration. METHODS After metformin urine samples were diluted by mobile phase, the supernatant was injected into the system directly by using Lichrospher ODS coLumn with a mobile phase of 3 mmoL/L sodium dodecylsulfate (pH 4)∶acetonitrile (75∶25),and the detection wavelength is 240 nm. Glipizide and IS were extracted by acetic ether after urine acidation, and separated on Lichrospher ODS column using acetonitrile and 0.1% acetic acid (10 mmoL?L-1ammonium acetate) (55∶45) as mobile phase. MS was performed in the selected anion monitoring mode. Ten health Chinese volunteers were treated with single dose of two metformin-glipizide tablets, the metformin and glipizide concentrations in urine were determined by the methods. RESULTS The inter-day and intra-day precision values were below 10%. In 24 h，the accumulation amounts of metformin and glipizide excreted in urine were 102.5 ± 27.3 mg、452.2 ± 191.4 μg, respectively, the accumulated excretion rates were 26.27 % ± 7.0 %, 9.04 % ± 3.83 %, respectively. CONCLUSIONS The assays have been proved to be accurate and sensitive, and can be used in the study of human urinary excretions of glipizide and metformin.

Key words: metformin, glipizide, LC-MS, HPLC, urinary excretion