Phentermine interference and high L-methamphetamine concentration problems in GC-EI-MS SIM analyses of R-(-)-α-methoxy-α (trifluoromethyl)phenylacetyl chloride-derivatized amphetamines and methamphetamines

摘要

In order to achieve chromatographic separation, urine samples shown to be initially positive for amphetamines and methamphetamines in US Department of Defense immunoassays are derivatized with R-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride (R-(-)-MTPA) prior to gas chromatography-electron impact-mass spectrometry (GC-EI-MS) analysis. Phentermine, a member of the phenethylamine class of drugs and a common appetite suppressant, interferes with GC-EI-MS assays of R-(-)-MTPA-derivatized D-amphetamine, degrading the chromatography of the internal standard and analyte ions and skewing concentration calculations. Additionally, when specimens with high concentrations of L-methamphetamine are derivatized with R-(-)-MTPA, signal peaks have the potential to be misidentified by integration software as D-methamphetamine. We have found that replacing R-(-) MTPA with (S)-(+)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride reduces phentermine interference problems related to internal standard chromatography, reduces the possibility of concentrated L-methamphetamine peaks being misidentified by integration software, improves resolution of D-methamphetamine in the presence of high L-methamphetamine concentrations, and is a cost-neutral change that can be applied to current amphetamines GC-EI-MS methods without the need for method modification.