PMID- 14656600
OWN - NLM
STAT- MEDLINE
DCOM- 20040921
LR  - 20191210
IS  - 0731-7085 (Print)
IS  - 0731-7085 (Linking)
VI  - 33
IP  - 5
DP  - 2003 Dec 4
TI  - HPLC-MS/MS determination of a peptide conjugate prodrug of doxorubicin, and its 
      active metabolites, leucine-doxorubicin and doxorubicin, in dog and rat plasma.
PG  - 1093-102
AB  - A HPLC-MS/MS Electrospray (ESI) method was developed and validated to quantify a 
      peptide conjugate prodrug of doxorubicin (Dox-Con) and its active metabolites 
      leucine-doxorubicin (Leu-Dox) and doxorubicin (Dox) in dog and rat plasma. The 
      analytes were extracted from plasma by solid-phase extraction on a Bond Elut C8 
      cartridge and eluted with chloroform-methanol (2:1). Eluates were evaporated and 
      reconstituted in acetonitrile-5 microM sodium trifluoroacetate in 0.1% aqueous 
      formic acid (20:80) and injected onto a Waters Oasis HLB column. Analytes were 
      eluted from the column with a solvent gradient into the mass analyzer. The ions 
      were quantified in the selected reaction-monitoring mode (SRM), using positive 
      ions, on a triple quadrupole mass spectrometer. The lower limits of 
      quantification for Dox-Con, Leu-Dox, and Dox in plasma, were approximately 5, 1 
      (dog)/6 (rat), and 0.5 ng/ml, respectively. Intra- and inter-assay accuracy (% of 
      nominal concentration) and precision (%CV) for all analytes were within 15 and 
      16%, respectively.
FAU - Mazuel, Claude
AU  - Mazuel C
AD  - Laboratoires Merck-Sharp and Dohme-Chibret Route de Marsat--Riom, 63963 
      Clermont-Ferrand Cedex 9, France. claude_mazuel@merck.com
FAU - Grove, Jeffrey
AU  - Grove J
FAU - Gerin, Genevieve
AU  - Gerin G
FAU - Keenan, Kevin P
AU  - Keenan KP
LA  - eng
PT  - Journal Article
PT  - Validation Study
PL  - England
TA  - J Pharm Biomed Anal
JT  - Journal of pharmaceutical and biomedical analysis
JID - 8309336
RN  - 0 (Peptides)
RN  - 0 (Prodrugs)
RN  - 80168379AG (Doxorubicin)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - Animals
MH  - Calibration
MH  - Chromatography, High Pressure Liquid/methods
MH  - Dogs
MH  - Doxorubicin/*blood/metabolism
MH  - Drug Stability
MH  - Female
MH  - Freezing
MH  - Leucine/*blood
MH  - Male
MH  - Peptides/*blood/metabolism
MH  - Prodrugs/analysis/*metabolism
MH  - Rats
MH  - Spectrometry, Mass, Electrospray Ionization/*methods
EDAT- 2003/12/06 05:00
MHDA- 2004/09/24 05:00
CRDT- 2003/12/06 05:00
PHST- 2003/12/06 05:00 [pubmed]
PHST- 2004/09/24 05:00 [medline]
PHST- 2003/12/06 05:00 [entrez]
AID - S0731708503004345 [pii]
AID - 10.1016/s0731-7085(03)00434-5 [doi]
PST - ppublish
SO  - J Pharm Biomed Anal. 2003 Dec 4;33(5):1093-102. doi: 
      10.1016/s0731-7085(03)00434-5.