Quantification of erufosine, the first intravenously applicable alkylphosphocholine, in human plasma by isotope dilution liquid chromatography–tandem mass spectrometry using a deuterated internal standard

Abstract

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 μM), 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 44.0 mg/L, respectively. The method has been used for analyses during a phase I clinical trial of ErPC 3.