PMID- 34159374
OWN - NLM
STAT- MEDLINE
DCOM- 20220715
LR  - 20220715
IS  - 1945-239X (Electronic)
IS  - 0021-9665 (Linking)
VI  - 60
IP  - 6
DP  - 2022 Jul 12
TI  - Simultaneous Monitoring of Azathioprine Metabolites in Erythrocytes of Crohn's 
      Disease Patients by HPLC-UV.
PG  - 518-524
LID - 10.1093/chromsci/bmab084 [doi]
AB  - The conversion of azathioprine (AZA) to active 6-thioguanine nucleotides (6-TGN) 
      is essential for its clinical efficacy; however, another metabolite formed, 
      6-methylmercaptopurine (6-MMP), is related to hepatotoxicity. Blood samples were 
      collected from 37 patients under AZA's treatment, and a new HPLC-UV method was 
      validated and applied for simultaneous quantification of 6-TGN and 6-MMP in 
      erythrocytes of Crohn's disease (CD) patients. The concentration of 6-TGN and 
      6-MMP found ranged from 4.5 to 2,456 rhomol/8 x 108 red blood cells (RBCs) for 
      6-TGN and from 170 to 53,951 rhomol/8 x 108 RBCs for 6-MMP. Reduced levels of 6-MMP 
      in patients into combo therapy with AZA and allopurinol (2,031 rhomol/8 x 108 RBCs) 
      have been observed when compared to patients undergoing monotherapy with AZA 
      (9,098 rhomol/8 x 108 RBCs). Additionally, there was a negative correlation (r = 
      -83.7%, P < 0.05) between lymphocyte count and 6-TGN levels. The method developed 
      is reliable, accurate and reproducible and can be used as an important tool in 
      the monitoring routine of patients with CD under AZA treatment, allowing the 
      individualization of the dose, monitoring adherence to the treatment and the 
      evaluation of the clinical outcome of these patients.
CI  - (c) The Author(s) 2021. Published by Oxford University Press. All rights reserved. 
      For Permissions, please email: journals.permissions@oup.com.
FAU - Ribeiro, Aline Correa
AU  - Ribeiro AC
AD  - Laboratory of Clinical and Experimental Pharmacology, Department of Pharmacology, 
      Federal University of Juiz de Fora, Jose Lourenco Kelmer, s/n degrees , 36360-900, Juiz 
      de Fora, Minas Gerais, Brazil.
FAU - Barroso, Luciane Henriques Furtado
AU  - Barroso LHF
AD  - Laboratory of Clinical and Experimental Pharmacology, Department of Pharmacology, 
      Federal University of Juiz de Fora, Jose Lourenco Kelmer, s/n degrees , 36360-900, Juiz 
      de Fora, Minas Gerais, Brazil.
FAU - Mourao-Junior, Carlos Alberto
AU  - Mourao-Junior CA
AD  - Department of Physiology, Federal University of Juiz de Fora, Jose Lourenco 
      Kelmer, s/n degrees , 36360-900, Juiz de Fora, Minas Gerais, Brazil.
FAU - Chebli, Julio Maria Fonseca
AU  - Chebli JMF
AD  - Division of Gastroenterology, Department of Internal Medicine, University 
      Hospital of the Federal University of Juiz de Fora and Monte Sinai Hospital, 
      Eugenio do Nascimento s/n degrees , 36038-330, Juiz de Fora, Minas Gerais, Brazil.
FAU - Nascimento, Jorge Willian Leandro
AU  - Nascimento JWL
AUID- ORCID: 0000-0002-0334-0217
AD  - Laboratory of Clinical and Experimental Pharmacology, Department of Pharmacology, 
      Federal University of Juiz de Fora, Jose Lourenco Kelmer, s/n degrees , 36360-900, Juiz 
      de Fora, Minas Gerais, Brazil.
LA  - eng
GR  - ConocoPhillips Company/
GR  - # APQ-03823-17/Brazilian Ministry of Health/
PT  - Journal Article
PL  - United States
TA  - J Chromatogr Sci
JT  - Journal of chromatographic science
JID - 0173225
RN  - 0 (Immunosuppressive Agents)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - *Azathioprine/adverse effects/therapeutic use
MH  - Chromatography, High Pressure Liquid
MH  - *Crohn Disease/drug therapy/metabolism
MH  - Erythrocytes/metabolism
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects/therapeutic use
EDAT- 2021/06/24 06:00
MHDA- 2022/07/16 06:00
CRDT- 2021/06/23 07:26
PHST- 2021/03/02 00:00 [received]
PHST- 2021/06/24 06:00 [pubmed]
PHST- 2022/07/16 06:00 [medline]
PHST- 2021/06/23 07:26 [entrez]
AID - 6307933 [pii]
AID - 10.1093/chromsci/bmab084 [doi]
PST - ppublish
SO  - J Chromatogr Sci. 2022 Jul 12;60(6):518-524. doi: 10.1093/chromsci/bmab084.