Simultaneous analysis of cardiac glycosides in blood and urine by thermoresponsive LC-MS-MS
Simultaneous analysis of cardiac glycosides in blood and urine by thermoresponsive LC-MS-MS
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热响应 LC-MS-MS 同时分析血液和尿液中的强心苷
DOI：
10.1007/s00216-010-4405-1
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Osamu Suzuki
中科院分区：
文献类型：
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作者：
Sanae Kanno;Kanako Watanabe;Itaru Yamagishi;Seishiro Hirano;Kayoko Minakata;Kunio Gonmori;Osamu Suzuki
采用一种新型温敏聚合物分离柱同时测定了人血和尿中4种广泛用于治疗心律失常和心力衰竭的强心苷。该柱由N-异丙基丙烯酰胺聚合物组成，其表面通过改变温度而经历从亲水性到疏水性的可逆改变。色谱分离和保留时间可以通过调节柱温来容易地控制。当柱温在8分钟内从50 °C变为10 °C时，包括去毛花苷、地高辛、甲基地高辛、洋地黄毒苷和洋地黄毒苷配基（内标）的五种CG被更好地分离。使用这些LC条件，我们分析了四个CG在人体全血和尿液中同时通过液相色谱-串联质谱（LC-MS-MS）。对验证数据（作为回收率、线性、准确度和精密度的函数）进行了仔细检测;所有数据均符合要求。两种基质中四种CG的检测限为0.2-0.3 ng/mL。方法已应用于实际尸检中甲基地高辛及其主要代谢产物地高辛的分析。据我们所知，这是第一个报告描述了LC-MS-MS方法使用的温度响应柱分析药物（S）。在LC-MS-MS技术中包含温敏柱似乎扩展了在有限的分析时间内同时分析生物样品中不同性质的化合物（如疏水前体及其亲水代谢物）的可能性。
A new thermoresponsive polymer separation column was applied to simultaneous analysis of four cardiac glycosides (CGs) being widely used for the treatment of arrhythmias and heart failure in human blood and urine. This column is composed of anN-isopropylacrylamide polymer, the surface of which undergoes a reversible alteration from hydrophilic to hydrophobic by changing temperature. The chromatographic separation and retention times can be easily be controlled by adjusting the column temperature. As the column temperature was changed from 50 to 10 °C over 8 min, five CGs, including deslanoside, digoxin, methyldigoxin, digitoxin, and digitoxigenin (internal standard) were better resolved. Using these LC conditions, we analyzed four CGs in human whole blood and urine simultaneously by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Validation data as functions of recovery rates, linearity, accuracy, and precision were carefully tested; all were generally satisfactory. The detection limits for the four CGs in both matrices were 0.2–0.3 ng/mL. The method was applied to analysis of methyldigoxin and its main metabolite digoxin in whole blood and urine samples obtained from a deceased person in actual autopsy case. To our knowledge, this is the first report describing an LC-MS-MS method using a thermoresponsive column for analysis of drug(s). The inclusion of the thermoresponsive column in an LC-MS-MS technique seems to extend the possibility for simultaneous analysis of compounds of different properties, such as hydrophobic precursors and their hydrophilic metabolites in biological samples within limited analysis times.