Enantioselective trace analysis of amphetamine in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry

A method for the quantitative enantioselective analysis of amphetamine in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry (GC/NICI‐MS) is presented. Five‐fold deuterated analogues of both enantiomers were used as internal standard. Plasma sample preparation was performed by a rapid liquid–liquid extraction using n‐hexane. Derivatization with ( S )‐( − )‐ N ‐(heptafluorobutyryl)prolyl chloride was accomplished directly in the n‐hexane extract to avoid loss of amphetamine during sample concentration. The method was validated in the expected concentration range of 0.006 for a pharmacokinetic study. Calibration curves were linear within a range 0.006–50 ng/mL plasma. Precision and accuracy were acceptable over the entire calibration range. Baseline separation of the enantiomers was easily achieved on a 15‐m nonchiral apolar column. The method is simple and robust, and has been applied to the batch analysis of amphetamine enantiomers. Copyright © 2003 John Wiley & Sons, Ltd.