同时测定人血浆中甲砜霉素和前药甲砜霉素甘氨酸酯浓度及其药代动力学研究

目的: 建立一种简单、灵敏同时测定人血浆中甲砜霉素(TAP)及其前药甲砜霉素甘氨酸酯(TG)的高效液相色谱法。方法: 24名健康志愿者随机分为三组,分别静脉滴注低(0.5 g)、中(1.0 g)、高(1.5 g)三个剂量的注射用盐酸甲砜霉素甘氨酸酯;采用乙酸乙酯萃取法处理血浆,色谱柱为 Hypersil ODS₂(5 μm,4.6 mm×200 mm 大连,依利特),流动相为乙腈-水(0.003 mol/L 四丁基溴化铵与 0.056 mol/L 乙酸铵) =13∶87(pH=6.6),流速为 1 mL/min,检测波长为 224 nm。结果: 血浆中TAP和TG标准曲线线性范围均为 0.78~100 μg/mL,高、中、低(0.78、6.25、100 μg/mL)三种浓度的日间和日内变异均小于 15.0％,血浆经室温 4 h 或者-70 ℃ 冷冻放置,冻融两次均显示TAP稳定性较好。结论: 该方法灵敏、准确、简单、快速,可用于TAP和TG的药代动力学研究。

Simultaneous determination of thiamphenicol and its prodrug thiamphenicol glycinate in human plasma and its pharmacokinetics study

AIM: To develop a simple and sensitive HPLC method for simultaneous determination of thiamphenicol (TAP) and its prodrug thiamphenicol glycinate (TG) in human plasma.METHODS: A single (0.5, 1.0, and 1.5 g) intravenous drip doses of thiamphenicol glycinate was performed on 24 Chinese healthy volunteers randomly. The plasma was treated with ethyl acetate.The chromatographic condition was as follows:a column of Hypersil ODS₂(5 μm, 4.6 mm×200 mm),a mobile phase consisting of acetonitrile-water containing 0.003 mol/L tetrabutyl ammonium bromide and 0.056 mol/L ammonium acetate (13∶87, pH=6.6) at a flow rate of 1 mL/min with UV detection at 224 nm.RESULTS: The calibration curves of TAP and TG were all linear ranging from 0.78 to 100 μg/mL in plasma and the intra-day and inter-day relative standard deviations were all less than 15％.TAP was stable in plasma samples after extraction or in two freeze-thaw cycles or in 4 h at ambient temperature or at -70 ℃.CONCLUSION: The method is sensitive, accurate, simple, fast and is suitable for the pharmacokinetics study of TAP and TG.