Determination of nonsteroidal anti-inflammatory drugs in human plasma by LC-MS-MS with a hydrophilic polymer column
Determination of nonsteroidal anti-inflammatory drugs in human plasma by LC-MS-MS with a hydrophilic polymer column
复制标题
DOI：
10.1007/s11419-010-0096-8
复制
发表时间：
2010-06
影响因子：
2.2
通讯作者：
X. Lee;T. Kumazawa;Chika Hasegawa;Tetsuya Arinobu;Akihito Kato;H. Seno;Keizo Sato
中科院分区：
文献类型：
--
作者：
X. Lee;T. Kumazawa;Chika Hasegawa;Tetsuya Arinobu;Akihito Kato;H. Seno;Keizo Sato
采用液相色谱-电喷雾串联质谱法（LC-MS-MS），采用亲水性聚合物柱（MSpak GF-310 4 B），直接进样生物样品，测定人血浆中6种非甾体抗炎药（NSAID）。采用10 mM乙酸铵/乙腈梯度洗脱法分离6种NSAID，即阿明洛芬、氟比洛芬、布洛芬、普拉洛芬、噻洛芬酸和扎托洛芬。通过LC-单级MS获得的质谱显示了阿明洛芬、扎托洛芬、噻洛芬酸和普拉洛芬的[M+H]+基峰离子，以及布洛芬和氟比洛芬的[M-H]-基峰离子。以串联模式从每个[M+H]+或[M-H]-离子产生产物离子。通过从正离子模式切换到负离子模式（反之亦然）的多反应监测进行定量。所有药物的加标回收率为77.0%~ 88.2%。6种药物的线性范围为0.01 ~ 25 μg/ml，检出限为0.002-0.005 μg/ml。定量限为0.01-0.02 μg/ml。血浆中所有药物的日内和日间变异系数均不大于8.1%。6种药物的定量准确度在94.5%~ 110%之间。还列出了口服给药后人血浆中阿明洛芬、普拉洛芬和布洛芬水平的实际测定数据。
Six nonsteroidal anti-inflammatory drugs (NSAIDs) in human plasma samples were analyzed by liquid chromatography (LC)-electrospray ionizationtandem mass spectrometry (MS-MS) using a hydrophilic polymer column (MSpak GF-310 4B), which enabled direct injection of crude biological samples. Separation of the six NSAIDs, alminoprofen, flurbiprofen, ibuprofen, pranoprofen, tiaprofenic acid, and zaltoprofen, was carried out using gradient elution with 10 mM ammonium acetate/acetonitrile. The mass spectra obtained by LC-single stage MS showed base peak ions due to [M+H]+for alminoprofen, zaltoprofen, tiaprofenic acid, and pranoprofen, and [M-H]-for ibuprofen and flurbiprofen. Product ions were produced from each [M+H]+or [M-H]-ion in the tandem mode. Quantitation was performed by multiple reaction monitoring with switching from positive to negative ion mode and vice versa. All drugs spiked into plasma showed recoveries of 77.0%–88.2%. The regression equations for the six drugs showed excellent linearity in the range of 0.01–25 μg/ml of plasma, and limits of detection were in the range of 0.002–0.005 μg/ml. Limits of quantitation were 0.01–0.02 μg/ml. Intraday and interday coeffi cients of variation for all drugs in plasma were not greater than 8.1%. The accuracy of quantitating the six drugs was in the range of 94.5%–110%. Data obtained from actual determinations of the levels of alminoprofen, pranoprofen, and ibuprofen in human plasma after oral administration are also presented.