Simultaneous Detection of Six Urinary Pteridines and Creatinine by High-Performance Liquid Chromatography-Tandem Mass Spectrometry for Clinical Breast Cancer Detection.

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Title: Simultaneous Detection of Six Urinary Pteridines and Creatinine by High-Performance Liquid Chromatography-Tandem Mass Spectrometry for Clinical Breast Cancer Detection.
Authors: Burton, Casey1, Honglan Shi1, Yinfa Ma1 yinfa@mst.edu
Source: Analytical Chemistry. 11/19/2013, Vol. 85 Issue 22, p11137-11145. 9p.
Subjects: Biomarkers, Biochemistry, Pteridines, Bicyclic compounds, Organonitrogen compounds, Breast cancer
Abstract: Recent preliminary studies have implicated urinary pteridines as candidate biomarkers in a growing number of malignancies including breast cancer. While the developments of capillary electrophoresis–laser induced fluorescence (CE-LIF), high performance liquid chromatography (HPLC), and liquid chromatography–mass spectroscopy (LC-MS) pteridine urinalyses among others have helped to enable these findings, limitations including poor pteridine specificity, asynchronous or nonexistent renal dilution normalization, and a lack of information regarding adduct formation in mass spectrometry techniques utilizing electrospray ionization (ESI) have prevented application of these techniques to a larger clinical setting. In this study, a simple, rapid, specific, and sensitive high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) method has been developed and optimized for simultaneous detection of six pteridines previously implicated in breast cancer and creatinine as a renal dilution factor in urine. In addition, this study reports cationic adduct formation of urinary pteridines under ESI-positive ionization for the first time. This newly developed technique separates and detects the following six urinary pteridines: 6-biopterin, 6-hydroxymethylpterin, d-neopterin, pterin, isoxanthopterin, and xanthopterin, as well as creatinine. The method detection limit for the pteridines is between 0.025 and 0.5 μg/L, and for creatinine, it is 0.15 μg/L. The method was also validated by spiked recoveries (81–105%), reproducibility (RSD: 1–6%), and application to 25 real urine samples from breast cancer positive and negative samples through a double-blind study. The proposed technique was finally compared directly with a previously reported CE-LIF technique, concluding that additional or alternative renal dilution factors are needed for proper investigation of urinary pteridines as breast cancer biomarkers. [ABSTRACT FROM AUTHOR]
Copyright of Analytical Chemistry is the property of American Chemical Society and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Label: Title
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  Data: Simultaneous Detection of Six Urinary Pteridines and Creatinine by High-Performance Liquid Chromatography-Tandem Mass Spectrometry for Clinical Breast Cancer Detection.
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  Data: <searchLink fieldCode="AR" term="%22Burton%2C+Casey%22">Burton, Casey</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Honglan+Shi%22">Honglan Shi</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Yinfa+Ma%22">Yinfa Ma</searchLink><relatesTo>1</relatesTo><i> yinfa@mst.edu</i>
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  Data: <searchLink fieldCode="JN" term="%22Analytical+Chemistry%22">Analytical Chemistry</searchLink>. 11/19/2013, Vol. 85 Issue 22, p11137-11145. 9p.
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  Data: <searchLink fieldCode="DE" term="%22Biomarkers%22">Biomarkers</searchLink><br /><searchLink fieldCode="DE" term="%22Biochemistry%22">Biochemistry</searchLink><br /><searchLink fieldCode="DE" term="%22Pteridines%22">Pteridines</searchLink><br /><searchLink fieldCode="DE" term="%22Bicyclic+compounds%22">Bicyclic compounds</searchLink><br /><searchLink fieldCode="DE" term="%22Organonitrogen+compounds%22">Organonitrogen compounds</searchLink><br /><searchLink fieldCode="DE" term="%22Breast+cancer%22">Breast cancer</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Recent preliminary studies have implicated urinary pteridines as candidate biomarkers in a growing number of malignancies including breast cancer. While the developments of capillary electrophoresis–laser induced fluorescence (CE-LIF), high performance liquid chromatography (HPLC), and liquid chromatography–mass spectroscopy (LC-MS) pteridine urinalyses among others have helped to enable these findings, limitations including poor pteridine specificity, asynchronous or nonexistent renal dilution normalization, and a lack of information regarding adduct formation in mass spectrometry techniques utilizing electrospray ionization (ESI) have prevented application of these techniques to a larger clinical setting. In this study, a simple, rapid, specific, and sensitive high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) method has been developed and optimized for simultaneous detection of six pteridines previously implicated in breast cancer and creatinine as a renal dilution factor in urine. In addition, this study reports cationic adduct formation of urinary pteridines under ESI-positive ionization for the first time. This newly developed technique separates and detects the following six urinary pteridines: 6-biopterin, 6-hydroxymethylpterin, d-neopterin, pterin, isoxanthopterin, and xanthopterin, as well as creatinine. The method detection limit for the pteridines is between 0.025 and 0.5 μg/L, and for creatinine, it is 0.15 μg/L. The method was also validated by spiked recoveries (81–105%), reproducibility (RSD: 1–6%), and application to 25 real urine samples from breast cancer positive and negative samples through a double-blind study. The proposed technique was finally compared directly with a previously reported CE-LIF technique, concluding that additional or alternative renal dilution factors are needed for proper investigation of urinary pteridines as breast cancer biomarkers. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
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  Data: <i>Copyright of Analytical Chemistry is the property of American Chemical Society and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1021/ac403124a
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      – Code: eng
        Text: English
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        PageCount: 9
        StartPage: 11137
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      – SubjectFull: Biomarkers
        Type: general
      – SubjectFull: Biochemistry
        Type: general
      – SubjectFull: Pteridines
        Type: general
      – SubjectFull: Bicyclic compounds
        Type: general
      – SubjectFull: Organonitrogen compounds
        Type: general
      – SubjectFull: Breast cancer
        Type: general
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      – TitleFull: Simultaneous Detection of Six Urinary Pteridines and Creatinine by High-Performance Liquid Chromatography-Tandem Mass Spectrometry for Clinical Breast Cancer Detection.
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            NameFull: Burton, Casey
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            NameFull: Honglan Shi
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            NameFull: Yinfa Ma
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            – D: 19
              M: 11
              Text: 11/19/2013
              Type: published
              Y: 2013
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