PMID- 21723208
OWN - NLM
STAT- MEDLINE
DCOM- 20111010
LR  - 20240321
IS  - 1873-376X (Electronic)
IS  - 1570-0232 (Print)
IS  - 1570-0232 (Linking)
VI  - 879
IP  - 23
DP  - 2011 Aug 1
TI  - Determination of hexamethylene bisacetamide, an antineoplastic compound, in mouse 
      and human plasma by LC-MS/MS.
PG  - 2206-12
LID - 10.1016/j.jchromb.2011.06.002 [doi]
AB  - Hexamethylene bisacetamide (HMBA) is a polar compound which has recently been 
      discovered to have antineoplastic activity by up-regulating the expression of an 
      endogenous antiproliferative breast cancer protein, HEXIM1 (hexamethylene 
      bisacetamide inducible protein 1) in vivo. HMBA has been shown in the past to 
      induce terminal differentiation in multiple leukemia types at a concentration of 
      2-5mM, but its phase I and II clinical trials were largely unsuccessful due to 
      serious side effects (notably, thrombocytopenia) with dose escalation. In this 
      work, a sensitive and simple LC-MS/MS method for direct determination of HMBA in 
      mouse and human plasma is described. Plasma samples were prepared by 
      deproteinization with acetonitrile. Separation was achieved on a Waters 
      Atlantis((R)) T3 (2.1 mm x 50 mm, 3 mum) column with retention times of 2.2 and 3.7 
      min for HMBA and 7MBA (internal standard), respectively. The quantitation was 
      carried out by tandem mass spectrometry using positive MRM mode. The linear range 
      of the method was 0.500-100 ng/mL in both mouse and human plasma with injection 
      volume of 5 muL. This method has been validated in accordance with the US Food and 
      Drug Administration (FDA) guidelines for bioanalytical method development and 
      applied to the determination of HMBA concentrations in FVB mice over time after a 
      single dose of HMBA in saline (0.9% NaCl) at 10mg/kg.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Smith, Kerri M
AU  - Smith KM
AD  - Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, 
      Cleveland, OH 44115, United States.
FAU - Ketchart, Wannarasmi
AU  - Ketchart W
FAU - Zhou, Xiang
AU  - Zhou X
FAU - Montano, Monica M
AU  - Montano MM
FAU - Xu, Yan
AU  - Xu Y
LA  - eng
GR  - R01 CA092440/CA/NCI NIH HHS/United States
GR  - CA92440/CA/NCI NIH HHS/United States
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20110613
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 (Acetamides)
RN  - 0 (Antineoplastic Agents)
RN  - LA133J59VU (hexamethylene bisacetamide)
SB  - IM
MH  - Acetamides/*blood
MH  - Animals
MH  - Antineoplastic Agents/*blood
MH  - Chromatography, Liquid/*methods
MH  - Humans
MH  - Male
MH  - Mice
MH  - Tandem Mass Spectrometry/*methods
PMC - PMC4068250
MID - NIHMS306962
EDAT- 2011/07/05 06:00
MHDA- 2011/10/11 06:00
PMCR- 2014/06/24
CRDT- 2011/07/05 06:00
PHST- 2010/11/18 00:00 [received]
PHST- 2011/06/03 00:00 [revised]
PHST- 2011/06/04 00:00 [accepted]
PHST- 2011/07/05 06:00 [entrez]
PHST- 2011/07/05 06:00 [pubmed]
PHST- 2011/10/11 06:00 [medline]
PHST- 2014/06/24 00:00 [pmc-release]
AID - S1570-0232(11)00376-X [pii]
AID - 10.1016/j.jchromb.2011.06.002 [doi]
PST - ppublish
SO  - J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Aug 1;879(23):2206-12. doi: 
      10.1016/j.jchromb.2011.06.002. Epub 2011 Jun 13.