title: GC-MS determination of amphetamine and methamphetamine in human urine for 12 hours following oral administration of dextro-methamphetamine: lack of evidence supporting the established forensic guidelines for methamphetamine confirmation.
abstract: Ten human volunteers, naive to amphetamines and divided into two groups of five each, were given an oral dose of 30 mg/70 kg D-methamphetamine in one of two different paradigms: the initial dose at 0930 h or the initial dose at 2130 h. One week later, each subject was crossed over with regard to time but given the same dose. A total of 214 urine specimens were collected either prior to dosing or at each micturition for a 12-h period post dose. Specimens were analyzed on a blind basis for methamphetamine and one of its metabolites, amphetamine, by gas chromatography-mass spectrometry (GC-MS) using coinjection of extracted sample and pentafluoropropionic anhydride and selected-ion monitoring. Approximately 20% of the D-methamphetamine was recovered unchanged from the urine specimens, and 2% was recovered as amphetamine. The mean urine methamphetamine concentration in both groups reached a maximum within 4-6 h and declined thereafter. A residual amount of methamphetamine was found in some predose specimens at the crossover evaluation, reflecting that methamphetamine may be detected in urine for up to 7 days. The amphetamine concentration reached a plateau by 4-6 h. This observation coupled with the finding that all subjects excreted approximately 2% of the methamphetamine dose as amphetamine suggested a saturable process for its biotransformation. Concentrations of both methamphetamine and amphetamine tended to be higher, but were not significantly different, for night administration. Methamphetamine concentrations were consistently greater than the 500-ng/mL cutoff in most post-dosing specimens, whereas amphetamine concentrations generally did not achieve the 200-ng/mL cutoff specified by the Substance Abuse and Mental Health Services Administration (SAMHSA) guidelines for GC-MS confirmation of methamphetamine. Some specimens containing methamphetamine had no amphetamine metabolite. The current guidelines would have resulted in 90.2% of the specimens containing methamphetamine being ruled negative by confirmation following either night or day administration, whereas one subject following the initial day administration and another following night crossover administration would have been judged positive at most time intervals. These findings suggest that the current SAMHSA guidelines select for individual metabolic variations and that GC-MS confirmation of methamphetamine will result in most occasional users being ruled negative following an oral dose of methamphetamine while some will be ruled positive.
authors.affiliation: Department of Pediatrics, University of Arkansas for Medical Sciences and Toxicology, Arkansas Children's Hospital, Little Rock 72202-3591, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Valentine
authors.forename: G L
authors.initials: GL
authors.lastname: Kearns
authors.forename: C
authors.initials: C
authors.lastname: Sparks
authors.forename: L G
authors.initials: LG
authors.lastname: Letzig
authors.forename: C R
authors.initials: CR
authors.lastname: Valentine
authors.forename: S A
authors.initials: SA
authors.lastname: Shappell
authors.forename: D F
authors.initials: DF
authors.lastname: Neri
authors.forename: C A
authors.initials: CA
authors.lastname: DeJohn
mesh_terms: D000284:Administration, Oral; D000661:Amphetamine / Q000652:urine*; D018592:Cross-Over Studies; D008401:Gas Chromatography-Mass Spectrometry; D017408:Guidelines as Topic; D006801:Humans; D008694:Methamphetamine / Q000008:administration & dosage / Q000652:urine*; D012015:Reference Standards; D013237:Stereoisomerism; D019966:Substance-Related Disorders; D014481:United States; D014482:United States Substance Abuse and Mental Health Services Administration
chemical_list: D008694:Methamphetamine; D000661:Amphetamine