Department of Chemistry, Missouri University of Science and Technology, Rolla, Missouri 65409, United States.
Phelps Health, Rolla, Missouri 65401, United States.
J Am Soc Mass Spectrom. 2020 Sep 2;31(9):1910-1917. doi: 10.1021/jasms.0c00181. Epub 2020 Aug 6.
Traumatic brain injury (TBI) is a serious public health concern for which sensitive and objective diagnostic methods remain lacking. While advances in neuroimaging have improved diagnostic capabilities, the complementary use of molecular biomarkers can provide clinicians with additional insight into the nature and severity of TBI. In this study, a panel of eight metabolites involved in distinct pathophysiological processes related to concussion was quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Specifically, the newly developed method can simultaneously determine urinary concentrations of glutamic acid, homovanillic acid, 5-hydroxyindoleacetic acid, methionine sulfoxide, lactic acid, pyruvic acid, -acetylaspartic acid, and F-isoprostane without intensive sample preparation or preconcentration. The method was systematically validated to assess sensitivity (method detection limits: 1-20 μg/L), accuracy (81-124% spike recoveries in urine), and reproducibility (relative standard deviation: 4-12%). The method was ultimately applied to a small cohort of urine specimens obtained from healthy college student volunteers. The method presented here provides a new technique to facilitate future work aiming to assess the clinical efficacy of these putative biomarkers for noninvasive assessment of TBI.
创伤性脑损伤（TBI）是一个严重的公共卫生问题，目前仍缺乏敏感和客观的诊断方法。尽管神经影像学的进步提高了诊断能力，但分子生物标志物的互补使用可以为临床医生提供更多关于 TBI 的性质和严重程度的见解。在这项研究中，使用高效液相色谱-串联质谱（HPLC-MS/MS）定量了一组涉及与脑震荡相关的不同病理生理过程的八种代谢物。具体来说，新开发的方法可以同时定量尿液中谷氨酸、高香草酸、5-羟色氨酸、甲硫氨酸亚砜、乳酸、丙酮酸、-乙酰天门冬氨酸和 F-异前列烷的浓度，而无需进行密集的样品制备或预浓缩。该方法经过系统验证，以评估其灵敏度（方法检测限：1-20μg/L）、准确性（尿液中 81-124%的加标回收率）和重现性（相对标准偏差：4-12%）。该方法最终应用于一组从健康大学生志愿者获得的小尿液标本。本文提出的方法为评估这些潜在生物标志物用于 TBI 无创评估的临床疗效提供了一种新技术。
