PMID- 29517997
OWN - NLM
STAT- MEDLINE
DCOM- 20180827
LR  - 20181207
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 23
IP  - 3
DP  - 2018 Mar 8
TI  - Sensitive Detection of 8-Nitroguanine in DNA by Chemical Derivatization Coupled 
      with Online Solid-Phase Extraction LC-MS/MS.
LID - 10.3390/molecules23030605 [doi]
LID - 605
AB  - 8-Nitroguanine (8-nitroG) is a major mutagenic nucleobase lesion generated by 
      peroxynitrite during inflammation and has been used as a potential biomarker to 
      evaluate inflammation-related carcinogenesis. Here, we present an online 
      solid-phase extraction (SPE) LC-MS/MS method with 6-methoxy-2-naphthyl glyoxal 
      hydrate (MTNG) derivatization for a sensitive and precise measurement of 8-nitroG 
      in DNA. Derivatization optimization revealed that an excess of MTNG is required 
      to achieve complete derivatization in DNA hydrolysates (MTNG: 8-nitroG molar 
      ratio of 3740:1). The use of online SPE effectively avoided ion-source 
      contamination from derivatization reagent by washing away all unreacted MTNG 
      before column chromatography and the ionization process in mass spectrometry. 
      With the use of isotope-labeled internal standard, the detection limit was as low 
      as 0.015 nM. Inter- and intraday imprecision was <5.0%. This method was compared 
      to a previous direct LC-MS/MS method without derivatization. The comparison 
      showed an excellent fit and consistency, suggesting that the present method has 
      satisfactory effectiveness and reliability for 8-nitroG analysis. This method was 
      further applied to determine the 8-nitroG in human urine. 8-NitroG was not 
      detectable using LC-MS/MS with derivatization, whereas a significant 
      false-positive signal was detected without derivatization. It highlights the use 
      of MTNG derivatization in 8-nitroG analysis for increasing the method 
      specificity.
FAU - Hu, Chiung-Wen
AU  - Hu CW
AD  - Department of Public Health, Chung Shan Medical University, Taichung 402, Taiwan. 
      windyhu@csmu.edu.tw.
FAU - Chang, Yuan-Jhe
AU  - Chang YJ
AUID- ORCID: 0000-0002-1851-0733
AD  - Department of Occupational Safety and Health, Chung Shan Medical University, 
      Taichung 402, Taiwan. handsom1005@gmail.com.
FAU - Chen, Jian-Lian
AU  - Chen JL
AD  - School of Pharmacy, China Medical University, Taichung 404, Taiwan. 
      cjl@mail.cmu.edu.tw.
FAU - Hsu, Yu-Wen
AU  - Hsu YW
AD  - Department of Occupational Safety and Health, Chung Shan Medical University, 
      Taichung 402, Taiwan. yayen0619@gmail.com.
AD  - Department of Optometry, Da-Yeh University, Changhua 515, Taiwan. 
      yayen0619@gmail.com.
FAU - Chao, Mu-Rong
AU  - Chao MR
AD  - Department of Occupational Safety and Health, Chung Shan Medical University, 
      Taichung 402, Taiwan. chaomurong@gmail.com.
AD  - Department of Occupational Medicine, Chung Shan Medical University Hospital, 
      Taichung 402, Taiwan. chaomurong@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20180308
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (8-nitroguanine)
RN  - 5Z93L87A1R (Guanine)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - *Chromatography, Liquid
MH  - DNA/analysis/*chemistry/genetics
MH  - DNA Damage
MH  - Guanine/*analogs & derivatives/analysis/chemistry
MH  - Reproducibility of Results
MH  - Sensitivity and Specificity
MH  - *Solid Phase Extraction
MH  - *Tandem Mass Spectrometry
PMC - PMC6017919
OTO - NOTNLM
OT  - LC-MS/MS
OT  - derivatization
OT  - isotope-dilution
OT  - nitrated DNA lesion
OT  - online solid-phase extraction
OT  - peroxynitrite
COIS- The authors declare no conflict of interest.
EDAT- 2018/03/09 06:00
MHDA- 2018/08/28 06:00
PMCR- 2018/03/08
CRDT- 2018/03/09 06:00
PHST- 2018/02/09 00:00 [received]
PHST- 2018/03/04 00:00 [revised]
PHST- 2018/03/06 00:00 [accepted]
PHST- 2018/03/09 06:00 [entrez]
PHST- 2018/03/09 06:00 [pubmed]
PHST- 2018/08/28 06:00 [medline]
PHST- 2018/03/08 00:00 [pmc-release]
AID - molecules23030605 [pii]
AID - molecules-23-00605 [pii]
AID - 10.3390/molecules23030605 [doi]
PST - epublish
SO  - Molecules. 2018 Mar 8;23(3):605. doi: 10.3390/molecules23030605.