Quantification of Candesartan in Mouse Plasma by MALDI-TOFMS and in Tissue Sections by MALDI-Imaging Using the Stable-Isotope Dilution Technique.
Quantification of Candesartan in Mouse Plasma by MALDI-TOFMS and in Tissue Sections by MALDI-Imaging Using the Stable-Isotope Dilution Technique.
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DOI：
10.5702/massspectrometry.a0021
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发表时间：
2013-01-01
期刊：
影响因子：
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通讯作者：
Takubo, Takayuki
中科院分区：
文献类型：
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作者：
Nakanishi, Toyofumi;Takai, Shinji;Takubo, Takayuki
为了测定坎地沙坦在小鼠血浆、血管和肾脏切片中的含量并更好地了解其药代动力学，我们应用基质辅助激光解吸/电离飞行时间质谱（MALDI-TOFMS）和MALDI-imaging mass spectrometry（IMS）与选择反应监测（SRM）模式，使用标记内标。基础检查结果显示，从方程得到的坎地沙坦血浆浓度曲线斜率为0.91，y轴截距为0.02。采用SRM模式的MALDI-TOFMS测定血浆中坎地沙坦的日内和日间准确度（n=10）和精密度分别在3.4%至17.3%和93.2%的范围内。坎地沙坦在血浆中的检出限为0.2nmol/L。IMS分析使我们能够澄清切片小鼠血管和肾脏切片中不同的空间时间分布图像，尽管它仍然需要改进定量方案。坎地沙坦在血浆和肾切片中具有典型的药代动力学模式，但在血管切片中，给药后24 h药代动力学模式逐渐增加。基质辅助激光解吸电离飞行时间质谱（MALDI-TOFMS）和离子质谱（IMS）结合固体火箭发动机（SRM）模式，是研究坎地沙坦在血管、组织切片和血浆中的空间分布和可追溯性的有力工具。
To determine the contents of candesartan in mouse plasma, and blood vessel and kidney sliced sections and also better understand its pharmacokinetics, we applied matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) and MALDI-imaging mass spectrometry (IMS) with the selected reaction monitoring (SRM) mode using a labeled-internal standard. The results of fundamental examinations showed that the slope of the resulting curves of candesartan in the plasma from the equation was 0.91 and the y-intercept was 0.02. Both intra- and inter-day accuracies (n=10) and the precision of candesartan in the plasma by MALDI-TOFMS with the SRM mode were in the range of 3.4 to 17.3% and 93.2%, respectively. The detection limit of candesartan in spiked plasma was 0.2nmol/L. IMS analysis enabled us to clarify distinct spacial time-distribution images in sliced mouse blood vessel and kidney sections although it still needed to improve a protocol of quantification. Typical pharmacokinetic patterns of candesartan were obtained in the plasma and sliced kidney sections, but those in the blood vessel sections gradually increased 24h after administration. MALDI-TOFMS and IMS with the SRM mode are powerful tools to identify the spacial distribution and traceability of candesartan in sliced blood vessel and tissue sections as well as in the plasma.