Optimization of Urinary Pteridine Analysis Conditions by CE-LIF for Clinical Use in Early Cancer Detection

Abstract

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 existing 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.

Department(s)

Chemistry

Sponsor(s)

Ellis Fischel Cancer Center
Foundation for Chemical Research
Missouri University of Science and Technology

Keywords and Phrases

6 Biopterin; 6 Hydroxymethylpterin; 6,7 Dimethylpterin; Neopterin; Pteridine; Pteridine Derivative; Unclassified Drug; Cancer Diagnosis; Capillary Electrophoresis; Controlled Study; Early Diagnosis; Fluorescence Analysis; Human; Laser Induced Fluorescence; Non Invasive Measurement; Oxidation; Process Optimization; Quantitative Analysis; Separation Technique; Statistical Significance; Urinalysis; Validation Process; Drug Stability; Early Detection Of Cancer; Electrophoresis, Capillary; Humans; Lung Neoplasms; Pteridines; Specimen Handling; Time Factors; CE; Conditional Study; Urinary Pteridine Analysis

International Standard Serial Number (ISSN)

0173-0835

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2009 Wiley-Blackwell, All rights reserved.

Publication Date

01 Oct 2009

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