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首页> 外文期刊>Journal of Neuroscience Methods >Simultaneous LC-MS/MS analysis of the biomarkers cAMP and cGMP in plasma, CSF and brain tissue
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Simultaneous LC-MS/MS analysis of the biomarkers cAMP and cGMP in plasma, CSF and brain tissue

机译：血浆，脑脊液和脑组织中生物标志物cAMP和cGMP的同时LC-MS / MS分析

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The cyclic nucleotides cyclic adenosine-3',5'-monophosphate (cAMP) and cyclic guanosine-3',5'-monophosphate (cGMP) are important second messengers. They are useful biomarkers to indicate biological activity of drugs such as phosphodiesterase (PDE) inhibitors which block the degradation of these nucleotides. Here, we established a fast and sensitive method for the simultaneous analysis of cAMP and cGMP by LC-MS/MS with broad applicability. The limit of detection is 50. pM. Linearity is given in a range of 0.5-500. nM for both nucleotides, with a high intra- and inter-assay precision and accuracy and an analysis time of 3.5. min. We validated the suitability of the method by pharmacological modulation of cAMP or cGMP concentrations in mice with the PDE4 inhibitor rolipram and the PDE5 inhibitor zaprinast. Rolipram significantly increased cAMP concentrations in plasma, CSF and brain tissue. Zaprinast increased cGMP concentrations in plasma but not in brain tissue, which is in accordance with its blood brain barrier permeability. In conclusion, the LC-MS/MS method described here could be a valuable analytical tool for investigating pharmacodynamic effects of PDE inhibitors and to monitor disease-related changes of cAMP and cGMP in the periphery as well as in the central nervous system.
机译：环状核苷酸环状腺苷3'，5'-单磷酸（cAMP）和环状鸟苷3'，5'-单磷酸（cGMP）是重要的第二信使。它们是有用的生物标记，用于指示可阻止这些核苷酸降解的药物（例如磷酸二酯酶（PDE）抑制剂）的生物活性。在这里，我们建立了一种快速灵敏的方法，通过LC-MS / MS同时分析cAMP和cGMP，具有广泛的适用性。检测极限是50. pM。线性范围为0.5-500。两个核苷酸均为nM，具有较高的测定内和测定间精度和准确度，分析时间为3.5。分钟我们通过药理学调节PDE4抑制剂咯利普兰和PDE5抑制剂扎必利斯特在小鼠中的cAMP或cGMP浓度，验证了该方法的适用性。咯利普兰显着增加血浆，脑脊液和脑组织中的cAMP浓度。 Zaprinast增加血浆中cGMP浓度，但不增加脑组织中的cGMP浓度，这与其血脑屏障通透性相符。总之，此处描述的LC-MS / MS方法可能是研究PDE抑制剂的药效学作用并监测外周及中枢神经系统中与疾病相关的cAMP和cGMP变化的有价值的分析工具。

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