title: 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†.
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.
authors.affiliation: Department of Chemistry, United States Naval Academy, Annapolis, MD, USA theron@usna.edu.
authors.forename: Theron J
authors.initials: TJ
authors.lastname: Hamilton
authors.affiliation: Department of Chemistry, United States Naval Academy, Annapolis, MD, USA.
authors.forename: Harry Z
authors.initials: HZ
authors.lastname: Qui
authors.affiliation: Department of Chemistry, United States Naval Academy, Annapolis, MD, USA.
authors.forename: Katherine V R
authors.initials: KV
authors.lastname: Dozier
authors.affiliation: United States Army Forensic Toxicology Drug Testing Laboratory, Fort Meade, MD, USA.
authors.forename: Zachary J
authors.initials: ZJ
authors.lastname: Fuller
mesh_terms: D000662:Amphetamines / Q000737:chemistry / Q000652:urine*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D008694:Methamphetamine / Q000737:chemistry / Q000652:urine; D008889:Military Personnel; D010645:Phentermine / Q000652:urine*; D010648:Phenylacetates / Q000737:chemistry*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D015813:Substance Abuse Detection / Q000379:methods*
chemical_list: D000662:Amphetamines; D010648:Phenylacetates; C101363:alpha-methoxy-alpha-trifluoromethylphenylacetyl chloride; D008694:Methamphetamine; D010645:Phentermine