Section for Pharmacology, Institute of Medicine, University of Bergen, 5021 Bergen, Norway.
Clin Chem. 2012 Feb;58(2):402-10. doi: 10.1373/clinchem.2011.174490. Epub 2011 Dec 22.
Biomarkers and metabolites related to B vitamin function and one-carbon metabolism have been studied as predictors of chronic diseases in studies based on samples stored in biobanks. For most biomarkers, stability data are lacking or fragmentary.
Degradation and accumulation kinetics of 32 biomarkers were determined at 23 °C in serum and plasma (EDTA, heparin, and citrate) collected from 16 individuals and stored for up to 8 days. In frozen serum (-25 °C), stability was studied cross-sectionally in 650 archival samples stored for up to 29 years. Concentration vs time curves were fitted to monoexponential, biexponential, linear, and nonlinear models.
For many biomarkers, stability was highest in EDTA plasma. Storage effects were similar at room temperature and at -25 °C; notable exceptions were methionine, which could be recovered as methionine sulfoxide, and cystathionine, which decreased in frozen samples. Cobalamin, betaine, dimethylglycine, sarcosine, total homocysteine, total cysteine, tryptophan, asymetric and symmetric dimethyl argenine, creatinine, and methylmalonic acid were essentially stable under all conditions. Most B vitamins (folate and vitamins B2 and B6) were unstable; choline increased markedly, and some amino acids also increased, particularly in serum. The kynurenines showed variable stability. For many biomarkers, degradation (folate and flavin mononucleotide) or accumulation (pyridoxal, riboflavin, choline, amino acids) kinetics at room temperature were non-first order.
Data on stability and deterioration kinetics for individual biomarkers are required to optimize procedures for handling serum and plasma, and for addressing preanalytical bias in epidemiological and clinical studies.
在基于生物库中储存样本的研究中，研究了与 B 族维生素功能和一碳代谢相关的生物标志物和代谢物，作为慢性疾病的预测因子。对于大多数生物标志物，稳定性数据缺乏或不完整。
在 23°C 下，从 16 个人采集的血清和血浆（EDTA、肝素和柠檬酸盐）中测定了 32 种生物标志物的降解和积累动力学，储存时间长达 8 天。在冷冻血清（-25°C）中，在储存时间长达 29 年的 650 个存档样本中进行了横断面稳定性研究。浓度与时间曲线拟合为单指数、双指数、线性和非线性模型。
对于许多生物标志物，EDTA 血浆中的稳定性最高。在室温下和-25°C 下，储存效应相似；显著的例外是蛋氨酸，它可以回收为蛋氨酸亚砜，胱氨酸在冷冻样本中减少。钴胺素、甜菜碱、二甲基甘氨酸、肌氨酸、总同型半胱氨酸、总半胱氨酸、色氨酸、不对称和对称二甲基精氨酸、肌酐和甲基丙二酸在所有条件下基本稳定。大多数 B 族维生素（叶酸和维生素 B2 和 B6）不稳定；胆碱显著增加，一些氨基酸也增加，特别是在血清中。色氨酸衍生物的稳定性不同。对于许多生物标志物，降解（叶酸和黄素单核苷酸）或积累（吡哆醛、核黄素、胆碱、氨基酸）动力学在室温下不是一级反应。
需要单个生物标志物的稳定性和降解动力学数据，以优化处理血清和血浆的程序，并解决流行病学和临床研究中的分析前偏倚。
