PMID- 24342897
OWN - NLM
STAT- MEDLINE
DCOM- 20150302
LR  - 20140715
IS  - 1536-3694 (Electronic)
IS  - 0163-4356 (Linking)
VI  - 36
IP  - 4
DP  - 2014 Aug
TI  - Immediate cooling does not prevent the ex vivo hydrolysis of L-asparagine by 
      asparaginase.
PG  - 549-52
LID - 10.1097/FTD.0000000000000030 [doi]
AB  - BACKGROUND: Monitoring of asparagine (ASN) during asparaginase (ASE) treatment 
      directly links to the antileukemic effect of ASE but is challenging because of 
      ASE-induced ex vivo hydrolysis of ASN. Assuming that ASE is not active at 4 degrees C, 
      immediate cooling of blood samples became the accepted method for ASN 
      determination during ASE therapy. METHODS: To evaluate the effect of immediate 
      sample cooling on the ex vivo hydrolysis of ASN by ASE the degradation of C4-ASN 
      in whole blood, spiked with different ASE concentrations were analyzed HPLC-MS. 
      C4-ASN and ASE were added either to blood at 4 degrees C or to blood at 37 degrees C, which was 
      instantly cooled down to 4 degrees C. RESULTS: Immediate cooling did not prevent the ex 
      vivo hydrolysis of ASN by ASE. The rate of ASN degradation to aspartic acid 
      depended on the amount of ASE, ASE preparation, and time. Spiked into blood at 
      4 degrees C 100 U/L native E. coli ASE already immediately degraded 100% of C4-ASN, 
      whereas 10 U/L reduced the amount of C4-ASN by 30%. Spiked into blood at 37 degrees C, 
      which was immediately cooled thereafter, 10 U/L native E. coli ASE hydrolyzed 60% 
      of C4-ASN and 1 U/L between 5% and 10% of C4-ASN. Concentrations of aspartic acid 
      increased in parallel with ASN degradation. In addition, the ex vivo hydrolysis 
      also affected concentrations of glutamine and glutamic acid. CONCLUSIONS: Cooling 
      of blood samples did not inactivate ASE. Thus, to evaluate the precise 
      pharmacodynamics of ASE, alternative methods for effective ASE inactivation at 
      the time of blood withdrawal are needed.
FAU - Lanvers-Kaminsky, Claudia
AU  - Lanvers-Kaminsky C
AD  - *Department of Pediatric Hematology and Oncology, University Children's Hospital 
      of Muenster, Muenster, Germany; and daggerLaboratory of Cancer Pharmacology, 
      Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, 
      Milan, Italy.
FAU - Westhoff, Petra Schulze
AU  - Westhoff PS
FAU - D'Incalci, Maurizio
AU  - D'Incalci M
FAU - Zucchetti, Massimo
AU  - Zucchetti M
FAU - Boos, Joachim
AU  - Boos J
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Ther Drug Monit
JT  - Therapeutic drug monitoring
JID - 7909660
RN  - 0 (Antineoplastic Agents)
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - 7006-34-0 (Asparagine)
RN  - EC 3.5.1.1 (Asparaginase)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Asparaginase/*pharmacology
MH  - Asparagine/*metabolism
MH  - Aspartic Acid/metabolism
MH  - Escherichia coli/metabolism
MH  - Humans
MH  - Hydrolysis/*drug effects
EDAT- 2013/12/18 06:00
MHDA- 2015/03/03 06:00
CRDT- 2013/12/18 06:00
PHST- 2013/12/18 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2015/03/03 06:00 [medline]
AID - 10.1097/FTD.0000000000000030 [doi]
PST - ppublish
SO  - Ther Drug Monit. 2014 Aug;36(4):549-52. doi: 10.1097/FTD.0000000000000030.