DETERMINATION OF ALFENTANIL AND NORALFENTANIL IN HUMAN PLASMA BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY

This report describes a simple gas chromatographic-mass spectrometric (GC-MS) assay for the simultaneous analysis of alfentanil and its major metabolite, noralfentanil, in human plasma. The method facilitates the processing of numerous samples for pharmacokinetic analysis. Alfentanil and noralfentanil are extracted from plasma under basic conditions and noralfentanil is converted to the pentafluoropropionyl derivative. The extraction efficiencies for noralfentanil and alfentanil were >99% and 70%, respectively. Standard curves were linear (r(2) = 0.99) over the ranges of 5-500 ng/ml for alfentanil and 0.4-10 ng/ml for noralfentanil. Inter-day coefficients of variation were 3.2% for alfentanil (50 ng/ml) and 3.1% for noralfentanil (1 ng/ml). This assay represents a significant improvement over existing HPLC assays which require radiolabelled alfentanil. The simultaneous disposition of alfentanil and noralfentanil in plasma after intravenous administration in humans is described.