Determination of a small, highly polar aminopropylphosphinic acid as racemate in plasma and urine and as separated enantiomers in plasma by liquid chromatography and tandem mass spectrometry Original Research Article

A fast and simple method for the determination of a γ-aminobutyric acid (GABA) receptor agonist, [R]-3-amino-2-fluoropropylphosphinic acid (I), in blood plasma and urine is described. This small and highly polar aminopropylphosphinic acid and an internal standard were isolated from the plasma sample after precipitation of the plasma proteins. Separation was achieved by liquid chromatography (LC) on a weak anion-exchanger as stationary phase and the analytes were measured by atmospheric-pressure positive ionization tandem mass spectrometry. The limit of quantification (LOQ) was 0.030 μmol l−1 with a repeatability of 8.3% at 0.067 μmol l−1 and below 2% above 1 μmol l−1. The urine samples were diluted with mobile phase after addition of the internal standard and assayed as the protein precipitated plasma samples. A chiral method for the determination of I and the S-enantiomer (II) in plasma, by means of derivatization with 1-fluoro-2,4-dinitrobenzene (DNFB) to the N-dinitrophenyl derivatives, after ultrafiltration is also presented. Finally, alternative LC-methods used for retaining the polar zwitterionic analytes are discussed.