Determination of gemifloxacin in different tissues of rat after oral dosing of gemifloxacin mesylate by LC-MS/MS and its application in drug tissue distribution study
Determination of gemifloxacin in different tissues of rat after oral dosing of gemifloxacin mesylate by LC-MS/MS and its application in drug tissue distribution study
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DOI：
10.1016/j.jpba.2009.12.019
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发表时间：
2010-06-05
影响因子：
3.4
通讯作者：
Pal, Tapan Kumar
中科院分区：
文献类型：
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作者：
Roy, Bikash;Das, Ayan;Pal, Tapan Kumar
建立了一种简便、灵敏、专属性强的液相色谱-串联质谱（LC-MS/MS）方法，用于评价吉米福在Wister白化病大鼠不同组织中的蓄积。该分析方法包括组织匀浆，然后进行简单的液-液萃取，并通过LC-MS/MS测定吉米福。分析物在Peerless basic C-18柱上分离（33 mm x 4.6 mm，3 μ m），含甲酸的甲醇-水等度移动的流动相（1.0%，v/v）MS/MS检测通过监测吉美氟沙星的m/z 390.100 -> 372.100和环丙沙星的m/z 332.100 -> 314.200的碎片来进行（内标; IS）。经验证的方法具有准确度、精密度和耐用性，在所有组织匀浆中具有良好的线性。在不同情况下分析的所有组织和血清的6组不同质控样品所得准确度和精密度值分别在91.833-102.283%和0.897- 5.291%范围内。该方法已成功地应用于吉美替尼的组织分布研究。目前的研究表明，吉美利嗪的最高组织浓度在肺中获得，（11.891纳克/克），其次是肝脏（10.110纳克/克），肾脏（10.095纳克/克），心脏（4.251纳克/克），睾丸多次口服200 mg甲磺酸吉非替尼7 d后3 h内，胃（3.182 ng/g）、脂肪组织（1.116 ng/g）和脑（0.982 ng/ml）的组织学变化。该方法也可用于大鼠组织中抗生素残留的组织分布模型研究和其他动物组织中抗生素残留的分析。(C)2010 Elsevier BV保留所有权利。
A simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to evaluate the accumulation of gemifloxacin in different tissues of Wister albino rat. The analytical method consists of the homogenization of tissues followed by simple liquid-liquid extraction and determination of gemifloxacin by an LC-MS/MS. The analyte was separated on a Peerless basic C-18 column (33 mm x 4.6 mm, 3 mu m) with an isocratic mobile phase of methanol-water containing formic acid (1.0%, v/v)(9:1, v/v) at a flow rate of 0.6 ml/min. The MS/MS detection was carried out by monitoring the fragmentation of m/z 390.100 -> 372.100 for gemifloxacin and m/z 332.100 -> 314.200 for ciprofloxacin (internal standard; IS) on a triple quadrupole mass spectrometer. The validated method was accurate, precise and rugged with good linearity in all tissue homogenates. The accuracy and precision value obtained from six different sets of quality control samples of all tissues and serum analyzed in separate occasions within 91.833-102.283% and 0.897-5.291%, respectively. The method has been successfully applied to tissue distribution studies of gemifloxacin. The present study demonstrates that the highest tissue concentration of gemifloxacin was obtained in lung (11.891 ng/g), followed by liver (10.110 ng/g), kidney (10.095 ng/g), heart (4.251 ng/g), testis (3.750 ng/g), stomach (3.182 ng/g), adipose tissue (1.116 ng/g) and brain (0.982 ng/ml) in 3 h after multiple oral dosing of 200 mg gemifloxacin mesylate for 7 days. This method may also be used for gemifloxacin tissue distribution modeling study in rat tissues and antibiotic residue analyses in other animal tissues. (C) 2010 Elsevier B.V. All rights reserved.