Simultaneous determination of L-dopa and its prodrug (S)-4-(2-acetamido-3-ethoxy-3-oxopropyl)-1,2-phenylene diacetate in rat plasma by high-performance liquid chromatography-tandem mass spectrometry and its application in a pharmacokinetic study

Simultaneous determination of L-dopa and its prodrug (S)-4-(2-acetamido-3-ethoxy-3-oxopropyl)-1,2-phenylene diacetate in rat plasma by high-performance liquid chromatography-tandem mass spectrometry and its application in a pharmacokinetic study
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高效液相色谱-串联质谱法同时测定大鼠血浆中左旋多巴及其前药(S)-4-(2-乙酰氨基-3-乙氧基-3-氧代丙基)-1,2-苯二乙酸酯及其含量

DOI:
10.1016/j.jpba.2010.05.003
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发表时间:
2010-11-02
影响因子:
3.4
通讯作者:
Xu, Chongyao
Xu, Chongyao
中科院分区:
医学3区
文献类型:
--
作者:
Jiang, Weizhe;Lv, Li;Xu, Chongyao

文献摘要

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建立了一种灵敏、简便、快速的高效液相色谱-串联质谱法(HPLC-MS/MS)同时测定左旋多巴及其前体药物(S)-4-本文研究了大鼠血浆中2-乙酰氨基-3-乙氧基-3-氧代丙基)-1,2-苯二乙酸酯(AEPD)的浓度(5 μ m,2.1 mm x 150 mm),采用安全防护C18柱(5 μ m,4 mm x 20 mm),并采用配备电喷雾电离(ESI)源的三重四极杆质谱进行检测。以α-甲基多巴为内标,样品预处理涉及用0.4 M高氯酸进行一步蛋白质沉淀。L-多巴和AEPD的线性范围分别为50-5000 ng/ml和12.5 -2500 ng/ml。超日和日间相对标准偏差(RSD)均小于15%,相对误差(RE)均小于15%。最后,该方法成功地应用于Sprague-Dawley大鼠口服左旋多巴及其前药AEPD后的药代动力学研究(C)2010 Elsevier B. V. All rights reserved
A sensitive, simple and rapid HPLC-MS/MS method has been developed and validated for the simultaneous determination of L-dopa and its prodrug (S)-4-(2-acetamido-3-ethoxy-3-oxopropyl)-1,2-phenylene diacetate (AEPD) in rat plasma in the present study The analytes were separated on a C(18) column (5 mu m, 2.1 mm x 150 mm) with a security guard C18 column (5 mu m, 4 mm x 20 mm) and a triple-quadrupole mass spectrometry equipped with an electrospray ionization (ESI) source was applied for detection. With alpha-methyldopa as internal standard, sample pretreatment involved in a one-step protein precipitation with 0.4 M perchloric acid. The method was linear over the concentration ranges of 50-5000 ng/ml for L-dopa and 12 5-2500 ng/ml for AEPD. The ultra-day and inter-day relative standard deviations (RSD) were less than 15% and the relative errors (RE) were all within 15%. Finally, the method was successfully applied to support the pharmacokinetic study after L-dopa and its prodrug AEPD were orally administrated to the Sprague-Dawley rats, respectively (C) 2010 Elsevier B.V. All rights reserved