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

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

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(0.5g)、中(1.0g)、高(1.5g)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(5μm,4.6mm×200mm大连,依利特),流动相为乙腈-水(0.003mol/L四丁基溴化铵与0.056mol/L乙酸铵)=13∶87(pH=6.6),流速为1mL/min,检测波长为224nm。结果:血浆中TAP和TG标准曲线线性范围均为0.78～100μg/mL,高、中、低(0.78、6.25、100μg/mL)三种浓度的日间和日内变异均小于15.0%,血浆经室温4h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。

AIM： To develop a simple and sensitive HPLC method for simultaneous deter- mination of thiamphenieol （TAP） and its pro- drug ttamphenicol 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 condi- tion was as follows：a column of Hypersil ODS2 （5um, 4.6 mmX200 mm）,a mobile phase con- sisting 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 at224 nm. RESULTS： The calibration curves of TAP and TG were all linear ranging from 0.78 to 100 ug/mL in plasma and the intra-day and inter-day relative standard deviations were all less than 15%. TAP was stable in plasma sam- ples after extraction or in two freeze-thaw cycles or in 4 h at ambient temperature or at --70 ℃. CONCLUSION： The method is sensitive, rate, simple, fast and is suitable for the ph cokinetics study of TAP and TG. aCCU arma-cokinetics study of TAP and TG.