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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†

Theron J Hamilton, Harry Z Qui, Katherine V R Dozier, Zachary J Fuller

J Anal Toxicol. 2014 Sep;38(7):456-61.

PMID: 24951536

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP20445334 (S)-(+)-α-Methoxy-α-(trifluoromethyl)phenylacetyl chloride (S)-(+)-α-Methoxy-α-(trifluoromethyl)phenylacetyl chloride 20445-33-4 Price
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