Direct-injection LC-MS-MS method for high-throughput simultaneous quantitation of simvastatin and simvastatin acid in human plasma
Direct-injection LC-MS-MS method for high-throughput simultaneous quantitation of simvastatin and simvastatin acid in human plasma
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DOI：
10.1016/s0731-7085(00)00309-5
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发表时间：
2000-08-15
影响因子：
3.4
通讯作者：
Powell, ML
中科院分区：
文献类型：
--
作者：
Jemal, M;Ouyang, Z;Powell, ML
建立了一种直接进样液相色谱-质谱-质谱（LC-RIS-MS）法，用于同时定量测定人血浆中广泛使用的降胆固醇前药辛伐他汀及其体内活性药物辛伐他汀酸。在简单地加入溶于水性缓冲液的内标溶液并浓缩后，将血浆样品进样至LC-MS-MS系统中。发现缓冲血浆样品中的分析物在4 ℃下可稳定至少24 h。在使用大量质控（QC）样品（包括辛伐他汀浓度与辛伐他汀酸浓度之比与校准曲线标准品中的浓度比不同的样品）的挑战性条件下，成功验证了该方法。在较低温度（4 ℃）和较低血浆pl-1（4.9）的双重稳定化条件下，辛伐他汀向辛伐他汀酸的过程中水解或辛伐他汀酸向辛伐他汀的内酯化降至≤ 1.0%。虽然在线净化和分析的整个运行时间仅为2.5 min，但实现了辛伐他汀与辛伐他汀酸的色谱基线分离，这是为了避免辛伐他汀酸对辛伐他汀选择的反应监测通道的干扰。仅进样8.0 μ l血浆样品即可达到所需的定量下限0.5 ng/ml。萃取柱持续至少500次进样。(C)2000 Elsevier Science B. V.保留所有权利。
A direct-injection liquid chromatography -mass spectrometry--mass spectrometry (LC-RIS-MS) method was developed and validated for the simultaneous quantitation in human plasma of the widely used cholesterol-lowering prodrug simvastatin and its in vivo generated active drug, simvastatin acid. The plasma samples were injected into the LC-MS-MS system after simply adding the internal standard solution in an aqueous buffer and centrifuging. The analytes in the buffered plasma samples were found to be stable For at least 24 h at 4 degrees C. The method was successfully validated under the challenging condition of using a large number of quality control (QC) samples including those in which the ratio of the simvastatin concentration to the simvastatin acid concentration was different from the concentration ratio in the calibration curve standards. Under the dual stabilizing conditions of lower temperature (4 degrees C) and lower plasma pl-l of 4.9, the in-process hydrolysis of simvastatin to simvastatin acid or the lactonization of simvastatin acid to simvastatin was minimized to less than or equal to 1.0%. Although the entire run time for on-line cleanup and analysis was only 2.5 min, chromatographic base-line separation of simvastatin from simvastatin acid, which was required to avoid the interference by simvastatin acid with the simvastatin selected reaction monitoring channel, was achieved. The desired lower limit of quantitation of 0.5 ng/ml was achieved by injecting only an equivalent of 8.0 mu l of the plasma sample. The extraction column lasted for at least 500 injections. (C) 2000 Elsevier Science B.V. All rights reserved.