Graça Gonçalo, Duarte Iola F, Goodfellow Brian J, Barros António S, Carreira Isabel M, Couceiro Ana Bela, Spraul Manfred, Gil Ana M
CICECO, Department of Chemistry, Campus UniversitArio de Santiago, University of Aveiro, 3810-193 Aveiro, Portugal.
Anal Chem. 2007 Nov 1;79(21):8367-75. doi: 10.1021/ac071278d. Epub 2007 Oct 6.
1D and 2D 800 MHz high-resolution nuclear magnetic resonance spectroscopy of human amniotic fluid (HAF) enabled the identification of approximately 50 metabolites. In addition, liquid chromatography-NMR and diffusion ordered spectroscopy (DOSY) allowed signal overlap to be reduced and the characterization of higher molecular weight (Mw) components, respectively. Indeed, the DOSY spectrum of a Mw >10 kDa HAF fraction enabled three protein families, differing in average Mw, to be detected and may therefore be of potential value in the study of disorder-related variations in HAF protein profiles. The effects of freeze-drying, storage at -20 or -70 degrees C, and freeze-thawing cycles on HAF compositional stability were investigated, as well as stability at room temperature (to account for overnight data acquisition runs). These data are the basis for establishing statistically validated correlations between HAF NMR data and any physiological disorders of the fetus/mother. Freeze-drying caused signal loss for urea, ethanol, and compounds resonating at 2.22 and 1.17 ppm. Storage at -70 degrees C or lower is recommended since only minor compositional changes were observed, affecting mainly acetate and pyruvate. Freeze-thaw cycles did not cause significant compositional changes, and room-temperature stability studies indicated a 4-5 h maximum period of handling/acquisition time to ensure HAF stability.
对人羊水(HAF)进行的一维和二维800兆赫高分辨率核磁共振波谱分析能够鉴定出大约50种代谢物。此外,液相色谱 - 核磁共振联用技术和扩散排序谱(DOSY)分别减少了信号重叠并实现了对高分子量(Mw)成分的表征。实际上,分子量大于10 kDa的HAF组分的DOSY谱图能够检测出三个平均分子量不同的蛋白质家族,因此在研究HAF蛋白质谱中与疾病相关的变化方面可能具有潜在价值。研究了冷冻干燥、在-20或-70摄氏度下储存以及冻融循环对HAF成分稳定性的影响,同时也研究了室温下的稳定性(以考虑过夜的数据采集过程)。这些数据是建立HAF核磁共振数据与胎儿/母亲任何生理疾病之间经统计学验证的相关性的基础。冷冻干燥导致尿素、乙醇以及在2.22和1.17 ppm处共振的化合物信号丢失。建议在-70摄氏度或更低温度下储存,因为仅观察到微小的成分变化,主要影响乙酸盐和丙酮酸盐。冻融循环未导致显著的成分变化,室温稳定性研究表明,为确保HAF的稳定性,处理/采集时间最长为4 - 5小时。