Quantification of erufosine, the first intravenously applicable alkylphosphocholine, in human plasma by isotope dilution liquid chromatography-tandem mass spectrometry using a deuterated internal standard.
A sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of erucylphosphohomocholine (erufosine, ErPC(3)) in pharmacokinetic studies. Nine-fold deuterated ErPC(3) was used as the internal standard. Following protein precipitation, reversed phase chromatography was performed. For analyte detection, electrospray ionization in the positive mode was applied. The mass transition m/z 504.4>139.1 was recorded for ErPC(3), and the transition m/z 513.7>139.1 for the internal standard, respectively. Good linearity with a correlation coefficient >0.99 was found for the range of 0.48-15 mg/L ErPC(3) in plasma (0.93-29.8 microM), the important range for clinical pharmacokinetic analysis. Interassay coefficients (n=10) of variation between 4.2% and 5.5% were found for ErPC(3) pool samples with concentrations between 4.7 mg/L and 44.0mg/L, respectively. The method has been used for analyses during a phase I clinical trial of ErPC(3).
Department of Internal Medicine III, Hospital of the University of Munich, Munich, Germany. Lars.Lindner@med.uni-muenchen.de
Lars H
LH
Lindner
Hansjoerg
H
Eibl
Martin
M
Hossann
Michael
M
Vogeser
D002853:Chromatography, Liquid / Q000379:methods* / Q000592:standards; D003903:Deuterium; D006801:Humans; D007201:Indicator Dilution Techniques; D007275:Injections, Intravenous; D010755:Organophosphates / Q000008:administration & dosage / Q000097:blood* / Q000592:standards; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000097:blood* / Q000592:standards; D012015:Reference Standards; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards
D010755:Organophosphates; D000644:Quaternary Ammonium Compounds; C472787:erucylphospho-N,N,N-trimethylpropylammonium; D003903:Deuterium