PMID- 27496503
OWN - NLM
STAT- MEDLINE
DCOM- 20170426
LR  - 20181202
IS  - 1873-2623 (Electronic)
IS  - 0041-1345 (Linking)
VI  - 48
IP  - 5
DP  - 2016 Jun
TI  - Determination of Concentrations of Azathioprine Metabolites 6-Thioguanine and 
      6-Methylmercaptopurine in Whole Blood With the Use of Liquid Chromatography 
      Combined With Mass Spectrometry.
PG  - 1836-9
LID - S0041-1345(16)00347-X [pii]
LID - 10.1016/j.transproceed.2016.01.084 [doi]
AB  - BACKGROUND: 6-Mercaptopurine (6-MP) and its prodrug azathioprine (AZA) are used 
      in many autoimmune diseases and after solid-organ transplantation. Their 
      properties are mediated by active metabolites, 6-thioguanine nucleotides (6-TGN), 
      and 6-methylmercaptopurine (6-MMP). The most common adverse effects are myelo- 
      and hepato-toxicity. The aim of the study was quantification of 6-TG and 6-MMP, 
      with the use of liquid chromatography combined with tandem mass spectrometry 
      (LC/MS/MS) in solid-organ transplant recipients. METHODS: In 33 patients, kidney 
      transplant recipient (n = 25) and liver transplant recipient (n = 8) 
      intra-erythrocyte concentrations of 6-TG and 6-MMP were measured with the use of 
      LC/MS/MS. RESULTS: The mean concentration of 6-TG was 205.35 +/- 157.62 pmol/8 x 
      10(8) red blood cells (RBC); median concentration of 6-MMP was 1064.1 
      (35.78-11,552.9) pmol/8 x 10(8) RBC. There were no correlations between 6-TG 
      levels and peripheral blood parameters (white blood cell count, WBC; hemoglobin, 
      Hb concentration; PLT, blood platelet count) or alanine aminotransferase activity 
      (AlAT) activity. Relationships between 6-MMP concentrations and peripheral blood 
      parameters (WBC, Hb, PLT) or AlAT activity have not been found. Subgroups with 
      leukopenia, anemia, thrombocytopenia, and liver dysfunction did not differ in 
      concentrations of 6-TG or 6-MMP. We have observed a negative correlation between 
      daily azathioprine dose and WBC count (r = -0.37, P = .04). CONCLUSIONS: 
      Relationships between concentrations of azathioprine metabolites and 
      myelotoxicity or hepatotoxicity have not been confirmed. Further studies on 
      larger groups of patients would be helpful in a more accurate understanding of 
      the impact of azathioprine metabolites on parameters of bone marrow and liver 
      function.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Zochowska, D
AU  - Zochowska D
AD  - Department of Immunology, Transplant Medicine, and Internal Diseases, Medical 
      University of Warsaw, Transplantation Institute, Warsaw, Poland.
FAU - Zegarska, J
AU  - Zegarska J
AD  - Department of Immunology, Transplant Medicine, and Internal Diseases, Medical 
      University of Warsaw, Transplantation Institute, Warsaw, Poland.
FAU - Hryniewiecka, E
AU  - Hryniewiecka E
AD  - Department of Clinical Nursing, Medical University of Warsaw, Warsaw, Poland.
FAU - Samborowska, E
AU  - Samborowska E
AD  - Institute of Biochemistry and Biophysics Polish Academy of Sciences, Warsaw, 
      Poland.
FAU - Jazwiec, R
AU  - Jazwiec R
AD  - Institute of Biochemistry and Biophysics Polish Academy of Sciences, Warsaw, 
      Poland.
FAU - Tszyrsznic, W
AU  - Tszyrsznic W
AD  - Institute of Biochemistry and Biophysics Polish Academy of Sciences, Warsaw, 
      Poland.
FAU - Borowiec, A
AU  - Borowiec A
AD  - Institute of Biochemistry and Biophysics Polish Academy of Sciences, Warsaw, 
      Poland.
FAU - Dadlez, M
AU  - Dadlez M
AD  - Institute of Biochemistry and Biophysics Polish Academy of Sciences, Warsaw, 
      Poland; Department of Biology, University of Warsaw, Warsaw, Poland.
FAU - Paczek, L
AU  - Paczek L
AD  - Department of Immunology, Transplant Medicine, and Internal Diseases, Medical 
      University of Warsaw, Transplantation Institute, Warsaw, Poland. Electronic 
      address: leszek.paczek@wum.edu.pl.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Transplant Proc
JT  - Transplantation proceedings
JID - 0243532
RN  - 0 (Guanine Nucleotides)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Thionucleotides)
RN  - 15867-02-4 (6-thioguanylic acid)
RN  - 6V404DV25O (6-methylthiopurine)
RN  - E7WED276I5 (Mercaptopurine)
RN  - FTK8U1GZNX (Thioguanine)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Adult
MH  - Azathioprine/adverse effects/metabolism
MH  - Chromatography, Liquid/methods
MH  - Erythrocytes/metabolism
MH  - Female
MH  - Guanine Nucleotides/*blood
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects/metabolism
MH  - Leukocyte Count
MH  - Male
MH  - Mercaptopurine/*analogs & derivatives/blood
MH  - *Organ Transplantation
MH  - Tandem Mass Spectrometry/methods
MH  - Thioguanine/*blood
MH  - Thionucleotides/*blood
EDAT- 2016/08/09 06:00
MHDA- 2017/04/27 06:00
CRDT- 2016/08/07 06:00
PHST- 2015/11/25 00:00 [received]
PHST- 2016/01/21 00:00 [accepted]
PHST- 2016/08/07 06:00 [entrez]
PHST- 2016/08/09 06:00 [pubmed]
PHST- 2017/04/27 06:00 [medline]
AID - S0041-1345(16)00347-X [pii]
AID - 10.1016/j.transproceed.2016.01.084 [doi]
PST - ppublish
SO  - Transplant Proc. 2016 Jun;48(5):1836-9. doi: 10.1016/j.transproceed.2016.01.084.