一种经过验证的采用苯甲酰氯衍生化法分析人脑脊液中神经递质代谢物的液相色谱-串联质谱法。
A validated LC-MS/MS method for neurotransmitter metabolite analysis in human cerebrospinal fluid using benzoyl chloride derivatization.
作者信息
Cox Jennifer M, Butler Jon P, Lutzke Barry S, Jones Barry A, Buckholz John E, Biondolillo Raymond, Talbot Jayne A, Chernet Eyassu, Svensson Kjell A, Ackermann Bradley L
机构信息
Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Q2 Solutions BioSciences, Ithaca, NY 14850, USA.
出版信息
Bioanalysis. 2015 Oct;7(19):2461-75. doi: 10.4155/bio.15.170. Epub 2015 Oct 16.
BACKGROUND
Human cerebrospinal fluid (CSF) is often acquired in Phase I clinical trials to assess the CNS penetration of new pharmacological agents and to search for biomarkers associated with PD effects. Robust methods for neurotransmitter metabolites in CSF have proven elusive, in part due to inadequate reversed phase LC retention.
RESULTS
Benzoyl chloride derivatization was used to promote retention for LC-MS/MS for a panel of neurotransmitter metabolites while delivering a concise method for sample preparation.
CONCLUSION
A validated assay in human CSF was obtained for 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3,4-dihydroxyphenylglycol and 5-hydroxyindoleacetic acid. This method is differentiated from other LC-MS/MS methods by delivering results in line with full regulatory expectations.
背景
在I期临床试验中，常采集人脑脊液（CSF）以评估新药理学药物的中枢神经系统渗透性，并寻找与帕金森病（PD）效应相关的生物标志物。用于脑脊液中神经递质代谢物的可靠方法一直难以实现，部分原因是反相液相色谱（LC）保留不足。
结果
使用苯甲酰氯衍生化来促进一组神经递质代谢物在LC-MS/MS中的保留，同时提供一种简洁的样品制备方法。
结论
获得了一种经过验证的人脑脊液中3,4-二羟基苯乙酸、高香草酸、3,4-二羟基苯乙二醇和5-羟基吲哚乙酸的检测方法。该方法与其他LC-MS/MS方法的不同之处在于，其结果符合全面的监管要求。
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