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Biomarkers Study of Errors of Metabolism by Coupling Chromatography with MS

Author: ZhaoJiYuan
Tutor: WangYiMing
School: Tsinghua University
Course: Chemistry
Keywords: Disease marker Gout Hyperuricemia Methylmalonic aciduria Liquid chromatography mass spectrometry
CLC: R446.11
Type: Master's thesis
Year: 2005
Downloads: 170
Quote: 0
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Abstract


The use of biological markers in the body content as disease diagnosis or health assessment basis, with objectivity is good, the advantages of high reliability, and can greatly facilitate the treatment of disease Evaluation. In this paper, gout, hyperuricemia and methylmalonic aciduria as the research object, a systematic study of these diseases in vivo biomarker information. Establish a method for determination of serum for 10 purine compound content of Mass Spectrometry UV quantitative HPLC-MS-MS method. The sensitivity and stability can meet the requirements of clinical testing. By measuring a certain number of patients with gout, hyperuricemia patients and normal serum samples, after statistical study found that two patients with serum uric acid, hypoxanthine and xanthine levels are associated with normal serum levels of three compounds There was a significant difference (p lt; 0.001), patients with gout and hyperuricemia in patients with serum xanthine (p lt; 0.01) and hypoxanthine (p lt; 0.001) levels were significantly different. Allopurinol treatment, two patients with serum uric acid, hypoxanthine and xanthine concentrations are decreased, the content difference is reduced, but gout patients hypoxanthine and xanthine content is higher than patients with hyperuricemia and wherein hypoxanthine levels exist significant differences (p lt; 0.01). z combination of all results hypoxanthine and xanthine is to distinguish between three types of people good biomarkers. It also established HPLC fingerprint method, principal component analysis and cluster analysis to distinguish between two types of patients and healthy subjects. The advantage of this method is that it allows the compound in serum more information can better reflect the status of the disease. Were established GC / MS and ESI-MS-MS determination of urinary methylmalonic acid levels approach. GC / MS method is advantageous in that the urine can be given a large spectrum of metabolites of information that can achieve a sample for many diseases, through the GC separation of the interference between the various substances, this method is very suitable for the detection of high-risk populations. ESI-MS-MS method suitable for large-scale screening newborns difference, without derivatization, two minutes to complete the testing of a sample. The results of both assays have shown that patients with urine methylmalonic acid content of methylmalonic acid 5-10 times normal. In the course of treatment, patients were followed urine methylmalonic acid levels can be used to evaluate the therapeutic effect.

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