Martens-Lobenhoffer Jens, Sulyok Endre, Czeiter Endre, Büki Andras, Kohl Jana, Firsching Raimund, Tröger Uwe, Bode-Böger Stefanie M
Institute of Clinical Pharmacology, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany.
J Neurosci Methods. 2007 Aug 15;164(1):155-60. doi: 10.1016/j.jneumeth.2007.04.005. Epub 2007 Apr 13.
Elevated cerebrospinal fluid (CSF) concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), are assumed to be related to delayed vasospasm after subarachnoid haemorrhage (SAH). However, data on CSF concentrations of L-arginine, ADMA and its structural isomer symmetric dimethylarginine (SDMA) are very sparse in humans. We here present a new hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS-MS) method for the precise determination of these substances in CSF. The method requires only minimal sample preparation and features isotope labeled internal standards. First data of patients with SAH showed that on the day of admission CSF concentration values of L-arginine and ADMA were not significantly different from controls, but increased markedly during the course of the hospital stay. The decrease of the L-arginine to ADMA ratio points to a progressive impairment of the NO production rate in the brain after SAH which is confirmed by a simultaneous decrease in nitrate and nitrite concentrations in CSF.
脑脊液（CSF）中不对称二甲基精氨酸（ADMA）水平升高，ADMA是一氧化氮合酶（NOS）的内源性抑制剂，被认为与蛛网膜下腔出血（SAH）后延迟性血管痉挛有关。然而，关于人体脑脊液中L-精氨酸、ADMA及其结构异构体对称二甲基精氨酸（SDMA）浓度的数据非常稀少。我们在此介绍一种新的亲水相互作用色谱-串联质谱（HILIC-MS-MS）方法，用于精确测定脑脊液中的这些物质。该方法仅需极少的样品制备，且具有同位素标记内标。SAH患者的首批数据显示，入院当天脑脊液中L-精氨酸和ADMA的浓度值与对照组无显著差异，但在住院期间显著升高。L-精氨酸与ADMA比值的降低表明SAH后大脑中NO生成率逐渐受损，这一点通过脑脊液中硝酸盐和亚硝酸盐浓度的同时降低得到证实。
