Optimization of urinary pteridine analysis conditions by CE-LIF for clinical use in early cancer detection

被引:28
作者
Gibbons, Stephen E.
Stayton, Isaac
Ma, Yinfa [1 ]
机构
[1] Missouri Univ Sci & Technol, Dept Chem, Rolla, MO 65409 USA
关键词
CE; Conditional study; Urinary pteridine analysis; INDUCED FLUORESCENCE DETECTION; CAPILLARY-ELECTROPHORESIS; VALIDATION; RISK;
D O I
10.1002/elps.200900077
中图分类号
Q5 [生物化学];
学科分类号
070307 [化学生物学];
摘要
The second leading cause of death in the US is cancer and early discovery of the disease has translated into reduced fatality rates. We have identified and performed a systematic investigation of a method for urinary pteridine analysis by using CE-LIF, which is believed to possess the potential to diagnose the presence of cancer even earlier than endsting methodologies. Through system enhancements, we have been able to improve the resolution of the two least resolved sets of peaks (6,7-dimethylpterin versus 6-biopterin and D-(+)-neopterin versus 6-hydroxymethylpterin) from 0.85 to 2.48 and 0.90 to 3.58, respectively. Additionally, we have discovered that the preparation of the urine samples in previous works was inadequate, and we have corrected the method to fully oxidize the pteridines in the urine, resulting in significantly less variability in quantification and greater ease of defining p-values for healthy versus cancer patients. Finally, we have performed validation steps of spike and recovery and short-term aging studies to demonstrate the method's robustness. As a result, we present an optimized and validated method ready for transfer from discovery phase to clinical trial that can potentially act as a non-invasively pre-screening test for cancer.
引用
收藏
页码:3591 / 3597
页数:7
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