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Enrichment and Quantitative Determination of 5-(hydroxymethyl)-2'Deoxycytidine, 5-(formyl)-2'-Deoxycytidine, and 5-(carboxyl)-2'Deoxycytidine in Human Urine of Breast Cancer by Magnetic Highcross-linked Microporous Polymers based on Poly-ionic Liquid Mengzhe Guo, Liyan Zhang, Yan Du, Wencheng Du, Dantong Liu, Cheng Guo, Yuanjiang Pan, and Dao-quan Tang Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.7b04755 • Publication Date (Web): 09 Jan 2018 Downloaded from http://pubs.acs.org on January 12, 2018
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Analytical Chemistry
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Enrichment and Quantitative Determination of 5-(hydroxymethyl)-
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2'-Deoxycytidine, 5-(formyl)-2'-Deoxycytidine, and 5-(carboxyl)-2'-
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Deoxycytidine in Human Urine of Breast Cancer by Magnetic High-
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cross-linked Microporous Polymers based on Poly-ionic Liquid
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Mengzhe Guo1§, Liyan Zhang1§, Yan Du1§, Wencheng Du1, Dantong Liu1, Cheng
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Guo3, Yuanjiang Pan2* and Daoquan Tang1*
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1
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou
Medical University, Xuzhou, Jiangsu 221004, China 2
Department of Chemistry, Zhejiang University, Hangzhou 310009, China
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Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of
Medicine, Hangzhou 310009, China §
These authors contributed equally to this work and should be considered co-first
authors
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*Corresponding author: Daoquan Tang
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Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou
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Medical College, Xuzhou, Jiangsu 221004, China
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E-mail address:
[email protected] 19
**Corresponding author: Yuanjiang Pan
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Department of Chemistry, Zhejiang University, Hangzhou 310009, China
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E-mail address:
[email protected] 22 23
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ABSTRACT
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5-(hydroxymethyl)-2'-deoxycytidine (5-hmdC), 5-(formyl)-2'-deoxycytidine (5-
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fodC), and 5-(carboxyl)-2'-deoxycytidine (5-cadC) are crucial intermediate products
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of DNA demethylation pathway, which can also act as potential biomarker reflecting
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the diagnosis and prognosis in multiple tumors. Detecting 5-hmdC, 5-fodC, and 5-
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cadC in human urine has various advantages including readily available samples and
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non-invasive to patients. However, few works have reported the detection of 5-fodC
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and 5-cadC due to their trace amounts. Here we developed a novel magnetic hyper-
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cross-linked microporous polymer (HMP) materials based on poly-ionic liquid (PIL)
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for the enrichment of 5-hmdC, 5-fodC, and 5-cadC. These magnetic PIL-HMP
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materials provided specific enrichment superiority for three modified cytidine. After
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enrichment, the signal intensity of 5-hmdC, 5-fodC, and 5-cadC increased 10~75
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folds with LLOQ of 0.049 ng/mL, 0.781 ng/mL, and 0.781 ng/mL respectively. The
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recoveries were approximately 86.5%~95.2% for 5-hmdC, 95.2%~107.8% for 5-fodC,
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and 99.4%~102.4% for 5-cadC under the relative standard deviation (RSD) of 0.2% to
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10.3%. Finally, we successfully applied magnetic PIL-HMP materials coupled with
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HPLC-ESI-MS/MS in enrichment and quantitative determination of 5-hmdC, 5-fodC,
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and 5-cadC in human urine of 10 breast cancer patients and 10 healthy people. We
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found that the level of 5-hmdC decreased in breast cancer patients (p
