PMID- 36233187
OWN - NLM
STAT- MEDLINE
DCOM- 20221017
LR  - 20221019
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 19
DP  - 2022 Oct 6
TI  - Improved HPLC Quantification of 6-Mercaptopurine Metabolites in Red Blood Cells: 
      Monitoring Data and Literature Analysis.
LID - 10.3390/ijms231911885 [doi]
LID - 11885
AB  - Thiopurine drugs azathioprine (AZA) and 6-mercaptopurine (6-MP) are used 
      extensively in pediatric and adult patients with inflammatory and neoplastic 
      diseases. They are metabolized to 6-thioguanine nucleotides (6-TGN) or to 
      6-methyl-mercaptopurine nucleotides (6-MMPN). The balance between 6-TGN and 
      6-MMPN is highly variable and monitoring is recommended, but its benefit in 
      outcome gives rise to conflicting results, potentially increased by differences 
      in quantifying 6-MP metabolism. Our aim was to report (1) the HPLC-UV procedure 
      used in our laboratory to quantify red blood cells (RBCs) with 6-TGN and 6-MMPN 
      (as its derivate: 6-MMP(d)) in patients treated with thiopurines and (2) 
      additional tests, sometimes confirmatory, to improve method standardization. The 
      comparison of two methods to count RBCs shows that metabolite concentrations were 
      slightly lower in the washed and resuspended RBCs than in whole blood. Perchloric 
      acid (0.7 M), dithiothreitol (DTT, final 0.013 M sample concentration) and 60 min 
      hydrolysis were selected for acid hydrolysis. (3) Monitoring data from 83 
      patients receiving AZA or 6-MP showed that at steady state, only 53/183 (29%) had 
      6-TGN and 6-MMPN in the recommended therapeutic range. Our method is discussed in 
      light of the technical conditions and sample stability data from 17 publications 
      identified since the first analytical report in 1987. Monitoring data 
      demonstrate, if required, that inter-patient variability in 6-TGN and 6-MMPN 
      concentrations is high in samples from treated patients.
FAU - Adam de Beaumais, Tiphaine
AU  - Adam de Beaumais T
AD  - Department of Biological Pharmacology and Pharmacogenetics, Hopital Saint-Louis, 
      Assistance Publique-Hopitaux de Paris, 1 rue Charles Vellefaux, 75011 Paris, 
      France.
FAU - Medard, Yves
AU  - Medard Y
AD  - Department of Biological Pharmacology and Pharmacogenetics, Hopital Saint-Louis, 
      Assistance Publique-Hopitaux de Paris, 1 rue Charles Vellefaux, 75011 Paris, 
      France.
FAU - Amblard, Oceane
AU  - Amblard O
AD  - Department of Biological Pharmacology and Pharmacogenetics, Hopital Saint-Louis, 
      Assistance Publique-Hopitaux de Paris, 1 rue Charles Vellefaux, 75011 Paris, 
      France.
FAU - Goldwirt, Lauriane
AU  - Goldwirt L
AD  - Department of Biological Pharmacology and Pharmacogenetics, Hopital Saint-Louis, 
      Assistance Publique-Hopitaux de Paris, 1 rue Charles Vellefaux, 75011 Paris, 
      France.
FAU - Simonin, Mathieu
AU  - Simonin M
AD  - Department of Pediatric Hematology and Oncology, Hopital Armand Trousseau, 
      Assistance Publique-Hopitaux de Paris, 26 Avenue du Docteur Arnold Netter, 75012 
      Paris, France.
AD  - Department of Education and Training, Sorbonne Universite, 1 rue Victor Cousin, 
      75005 Paris, France.
FAU - Martinez Vinson, Christine
AU  - Martinez Vinson C
AD  - Department of Pediatric Gastroenterology and Nutrition, Hopital Robert Debre, 
      Assistance Publique-Hopitaux de Paris, 48 Boulevard Serurier, 75018 Paris, 
      France.
FAU - Petit, Arnaud
AU  - Petit A
AUID- ORCID: 0000-0001-8363-1622
AD  - Department of Pediatric Hematology and Oncology, Hopital Armand Trousseau, 
      Assistance Publique-Hopitaux de Paris, 26 Avenue du Docteur Arnold Netter, 75012 
      Paris, France.
AD  - Department of Education and Training, Sorbonne Universite, 1 rue Victor Cousin, 
      75005 Paris, France.
FAU - Jacqz-Aigrain, Evelyne
AU  - Jacqz-Aigrain E
AD  - Department of Biological Pharmacology and Pharmacogenetics, Hopital Saint-Louis, 
      Assistance Publique-Hopitaux de Paris, 1 rue Charles Vellefaux, 75011 Paris, 
      France.
AD  - Department of Education and Training, Universite de Paris, 2 rue Albert Einstein, 
      75013 Paris, France.
LA  - eng
PT  - Journal Article
DEP - 20221006
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Nucleotides)
RN  - E7WED276I5 (Mercaptopurine)
RN  - FTK8U1GZNX (Thioguanine)
RN  - MRK240IY2L (Azathioprine)
RN  - T8ID5YZU6Y (Dithiothreitol)
SB  - IM
MH  - Adult
MH  - Azathioprine/metabolism
MH  - Child
MH  - Chromatography, High Pressure Liquid/methods
MH  - Dithiothreitol
MH  - Erythrocytes/metabolism
MH  - Humans
MH  - Immunosuppressive Agents/therapeutic use
MH  - *Inflammatory Bowel Diseases/metabolism
MH  - *Mercaptopurine/therapeutic use
MH  - Nucleotides/metabolism
MH  - Thioguanine/therapeutic use
PMC - PMC9570176
OTO - NOTNLM
OT  - 6-mercaptopurine
OT  - 6-thiopurines
OT  - acute leukemia
OT  - chronic inflammatory bowel disease
OT  - monitoring
OT  - pharmacogenetics
OT  - thiopurines
COIS- The authors declare no conflict of interest.
EDAT- 2022/10/15 06:00
MHDA- 2022/10/18 06:00
PMCR- 2022/10/06
CRDT- 2022/10/14 02:13
PHST- 2022/08/25 00:00 [received]
PHST- 2022/09/23 00:00 [revised]
PHST- 2022/09/27 00:00 [accepted]
PHST- 2022/10/14 02:13 [entrez]
PHST- 2022/10/15 06:00 [pubmed]
PHST- 2022/10/18 06:00 [medline]
PHST- 2022/10/06 00:00 [pmc-release]
AID - ijms231911885 [pii]
AID - ijms-23-11885 [pii]
AID - 10.3390/ijms231911885 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Oct 6;23(19):11885. doi: 10.3390/ijms231911885.