PMID- 31809961
OWN - NLM
STAT- MEDLINE
DCOM- 20200303
LR  - 20200303
IS  - 1873-376X (Electronic)
IS  - 1570-0232 (Linking)
VI  - 1136
DP  - 2020 Jan 1
TI  - Highly sensitive and rapid determination of azathioprine metabolites in whole 
      blood lysate by liquid chromatography-tandem mass spectrometry.
PG  - 121802
LID - S1570-0232(19)31085-2 [pii]
LID - 10.1016/j.jchromb.2019.121802 [doi]
AB  - Individualized therapy involves genetic test of drug metabolism, which provides 
      information about the initial dose and therapeutic drug monitoring for adjusting 
      the subsequent dose. Consequently, toxic side effects are expected to be 
      minimized and therapeutic effects to be maximized. In this study, an 
      ultra-performance liquid chromatography tandem mass spectrometry method that was 
      specific, accurate and sensitive was developed to simultaneously determine 
      azathioprine two metabolites, 6-thioguanine nucleotides (6-TGN) and 
      6-methyl-mercaptopurine riboside (6-MMPr) in the whole blood lysate. We 
      precipitated the sample by trifluoroacetic acid under the protection of 
      dithiothreitol, with 6-MMPr and 6-TGN being hydrolyzed to produce 
      6-methymercaptopurine and 6-thioguanine. In the chromatographic separation, 
      Waters ACQUITY BEH C18 (2.1 x 100 mm, 1.7 mum) chromatographic column was applied 
      and gradient elution was conducted with 0.02 mol/L ammonium acetate buffer (which 
      contains 0.3% formic acid) and acetonitrile at a flow rate of 0.4 ml/min. Tandem 
      mass spectrometry in multiple reaction monitoring mode was applied for detection 
      via electrospray ionization source in positive ionization mode. The analyzing 
      process lasted for no more than 2 min. The calibration curve for each metabolite 
      fitted a least squares model (weighed 1/X) from 1.25 to 5000 ng/ml (r(2) > 0.99). 
      The ion pairs were detected as 6-MMP m/z 167.07 --> 152.15, 6-TG m/z 
      168.06 --> 134.13, and internal standard m/z 171.07 --> 137.14. Under the guidance of 
      FDA guidelines for bioanalytical method validation, we carried out validation and 
      obtained satisfactory results. The method was successfully utilized for 
      monitoring the concentrations of each metabolite from 65 affected patients who 
      had received azathioprine maintenance therapy and achieved optimal results.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Miao, Qiang
AU  - Miao Q
AD  - Department of Laboratory Medicine/Research Center of Clinical Laboratory 
      Medicine, West China Hospital of Sichuan University, Chengdu, China.
FAU - Bai, Yang-Juan
AU  - Bai YJ
AD  - Department of Laboratory Medicine/Research Center of Clinical Laboratory 
      Medicine, West China Hospital of Sichuan University, Chengdu, China.
FAU - Zhang, Jun-Long
AU  - Zhang JL
AD  - Department of Laboratory Medicine/Research Center of Clinical Laboratory 
      Medicine, West China Hospital of Sichuan University, Chengdu, China.
FAU - Li, Yi
AU  - Li Y
AD  - Department of Laboratory Medicine/Research Center of Clinical Laboratory 
      Medicine, West China Hospital of Sichuan University, Chengdu, China.
FAU - Su, Zhen-Zhen
AU  - Su ZZ
AD  - Department of Laboratory Medicine/Research Center of Clinical Laboratory 
      Medicine, West China Hospital of Sichuan University, Chengdu, China.
FAU - Yan, Lin
AU  - Yan L
AD  - Department of Laboratory Medicine/Research Center of Clinical Laboratory 
      Medicine, West China Hospital of Sichuan University, Chengdu, China.
FAU - Wang, Lan-Lan
AU  - Wang LL
AD  - Department of Laboratory Medicine/Research Center of Clinical Laboratory 
      Medicine, West China Hospital of Sichuan University, Chengdu, China.
FAU - Zou, Yuan-Gao
AU  - Zou YG
AD  - Department of Laboratory Medicine/Research Center of Clinical Laboratory 
      Medicine, West China Hospital of Sichuan University, Chengdu, China. Electronic 
      address: immune_hx@126.com.
LA  - eng
PT  - Journal Article
DEP - 20190913
PL  - Netherlands
TA  - J Chromatogr B Analyt Technol Biomed Life Sci
JT  - Journal of chromatography. B, Analytical technologies in the biomedical and life 
      sciences
JID - 101139554
RN  - 0 (Guanine Nucleotides)
RN  - 0 (Thionucleotides)
RN  - 15867-02-4 (6-thioguanylic acid)
RN  - 342-69-8 (Methylthioinosine)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Adult
MH  - Azathioprine/*blood/*metabolism
MH  - Chromatography, High Pressure Liquid/*methods
MH  - Drug Monitoring/*methods
MH  - Female
MH  - Guanine Nucleotides/blood/metabolism
MH  - Humans
MH  - Limit of Detection
MH  - Linear Models
MH  - Male
MH  - Methylthioinosine/blood/metabolism
MH  - Middle Aged
MH  - Reproducibility of Results
MH  - Tandem Mass Spectrometry/*methods
MH  - Thionucleotides/blood/metabolism
OTO - NOTNLM
OT  - Azathioprine
OT  - Individualized therapy
OT  - Therapeutic drug monitoring
OT  - UPLC-MS/MS
EDAT- 2019/12/07 06:00
MHDA- 2020/03/04 06:00
CRDT- 2019/12/07 06:00
PHST- 2019/07/16 00:00 [received]
PHST- 2019/09/10 00:00 [revised]
PHST- 2019/09/11 00:00 [accepted]
PHST- 2019/12/07 06:00 [pubmed]
PHST- 2020/03/04 06:00 [medline]
PHST- 2019/12/07 06:00 [entrez]
AID - S1570-0232(19)31085-2 [pii]
AID - 10.1016/j.jchromb.2019.121802 [doi]
PST - ppublish
SO  - J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Jan 1;1136:121802. doi: 
      10.1016/j.jchromb.2019.121802. Epub 2019 Sep 13.