Quantitation of suspensions (MESED). Application of MESED-gC/MS in the quantitation of ifosfamide mustard in erythrocytes, plasma, and plasma water

Abstract

Compounds associated with particles in suspension are difficult to quantitate in the analysis of drugs in red blood cells. Breakthrough experiments were performed for the determination of a mustard gas related substance, ifosfamide mustard, originating from the anticancer agent ifosfamide. It is shown that the use of the measurement of sediment (MESED) instrument enables a comparison of ifosfamide mustard levels in red blood cells, total plasma, and plasma water. Red blood cell sediments were analysed by GC/MS together with plasma and plasma water extracts. The MESED maintains a direct relationship between the volume and weight of red blood cell sediments without disturbance of the equilibrium of a substance between the cells and the plasma, the latter being the suspending fluid. The MESED GC/MS combination has been applied successfully in clinical settings, estimating the importance of the red blood cell, plasma, and plasma water fractions in the presentation of ifosfamide mustard to other tissues by the blood. The presence of ifosfamide and ifosfamide mustard in red blood cells, total plasma, and plasma water was confirmed by negative chemical ionisation (NCI) mass spectrometry of the trifluoroacetylated derivatives following capillary GC. The NCI-Mass spectra of ifosfamide, ifosfamide mustard, and the internal standard cyclophosphamide provide specific fragment ion masses, which can be used in single or double ion monitoring of the substances for quantitation of cancer patient samples.