Liquid chromatography-electrospray tandem mass spectrometric assay suitable for quantitation of halofuginone in plasma.
An LC-MS/MS method was developed to quantitate the potential antitumor agent halofuginone in plasma. The assay uses 0.2 ml of plasma; chlorohalofuginone internal standard; acetonitrile for protein precipitation; a Phenomenex SYNERGI 4 micro Polar RP 80A (4 microm, 100 mm x 2 mm) column; an isocratic mobile phase of methanol:water:formic acid (80:20:0.02, v/v/v); and positive-ion electrospray ionization with selective reaction monitoring detection. Halofuginone eluted at approximately 2.4 min, internal standard eluted at approximately 2.9 min, and no endogenous materials interfered with their measurement. The assay was accurate, precise, and linear between 0.1 and 100 ng/ml. Halofuginone could be quantitated in dog plasma for at least 24 h after an i.v. dose of 0.1mg/kg. The assay is being used in ongoing pharmacokinetic studies of halofuginone.
Parise
Robert A
RA
Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, Room G27e, Hillman Research Pavilion, 5117 Centre Avenue, Pittsburgh, PA 15213-1863, USA.
Sparrow
Barney R
BR
Merrill
John W
JW
Grossi
Irma M
IM
Covey
Joseph M
JM
Peggins
James O
JO
Egorin
Merrill J
MJ
D000818:Animals; D002853:Chromatography, Liquid; D003049:Coccidiostats / Q000097:blood* / Q000493:pharmacokinetics; D004285:Dogs; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D008970:Molecular Weight; D010880:Piperidines; D011799:Quinazolines / Q000097:blood* / Q000493:pharmacokinetics; D052999:Quinazolinones; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization
D003049:Coccidiostats; D007202:Indicators and Reagents; D010880:Piperidines; D011799:Quinazolines; D052999:Quinazolinones; C010176:halofuginone