http://jat.oxfordjournals.org/content/36/9/634.full

A) Synthesized in 1887, amphetamine (1-methyl-2-phenethylamine) was the first member of a group of compounds that have similar structures and biological properties and are collectively called “amphetamines”. The group also includes methamphetamine, synthesized six years later, and 3-4 methyl-enedioxymethamphetamine (MDMA), patented in 1914.

Plasma concentrations of amphetamine (136 +/- 21 ng/ml) matched the levels reported in human ADHD patients (120 to 140 ng/ml) after amphetamine treatments that lasted for 3 weeks27 or 6 weeks. Both monkey species treated in this way developed 30-50% reductions in striatal dopamine, its major metabolite dihydroxy-phenylacetic acid, its rate-limiting enzyme (tyrosine hydroxylase), DAT, and VMAT. Other evidence suggests that non-human primates may be more vulnerable than rodents to stimulant-induced neurotoxicity.

By Berman S et al. Abuse of Amphetamines and Structural Abnormalities in Brain. Ann N Y Acad Sci. 2008 ; 1141: 195–220.

B) Oral fluid (OF) is a suitable alternative matrix to test drugs of abuse in clinical, workplace, driving under the influence of drugs (DUID), drug treatment, and criminal justice settings. The main advantages of OF are the simplicity and noninvasiveness of sample collection, which can be easily observed , obviating the need for special restroom facilities and same-sex collectors and making adulteration more difficult . Infection risk is lower than for blood , and OF may better reflect recent drug use.

The parent drug is frequently prominent in OF and may reflect free plasma concentrations, providing a better correlation with pharmacodynamic effects, such as impaired performance . It is difficult to differentiate heroin from morphine or codeine ingestion with urine drug testing, whereas 6- acetylmorphine (6AM) and heroin are frequently present in OF, clearly delineating heroin abuse.

Weak bases are detected in higher concentrations and for longer times in OF than in plasma because of ion trapping. Depending on a drug’s pKa and lipophilicity, ion trapping occurs because of pH differences in blood (7.4) and OF . Free uncharged drug is in equilibrium across membranes separating blood and OF. At the lower OF pH, weak bases ionize, increasing total OF drug concentrations. For clinical toxicology applications, including drug treatment, physician office, and emergency room testing, onsite OF testing offers rapid availability of results for diagnostic purposes and ability to confront treatment patients with immediate indicators of drug . In 2004, Substance Abuse and Mental Health Services Administration (SAMHSA) proposed recommended guidelines for mandated federal workplace OF testing.

By Bosker WM and Huestis MA. Oral Fluid Testing for Drugs of Abuse. Clin Chem. 2009 ; 55(11): 1910–1931.

C) Methamphetamine (MAMP) is a widely abused psychostimulant containing a chiral center, resulting in d-MAMP and l-MAMP enantiomers, with the d-MAMP isomer the more potent central nervous system stimulant.

The drug's composition is critical for results interpretation. For example, famprofazone is prescribed as a racemic mixture, which is metabolized to both d- and l-MAMP and AMP. D Benzphetamine is metabolized to d-MAMP and d-AMP, whereas l-selegeline is metabolized to l-MAMP and l-AMP. While results from famprofazone and benzphetamine administration can-not rule out illegal MAMP ingestion without supportive information, results from selegeline administration could prove legal ingestion because of the absence of d-MAMP and d-AMP. It is therefore essential to resolve MAMP and AMP enantiomers in order to more accurately interpret results.

By Newmeyer MN et al. Rapid Quantitative Chiral Amphetamines Liquid Chromatography-Tandem Mass Spectrometry Method in Plasma and Oral Fluid with a Cost-effective Chiral Derivatizing Reagent . J Chromatogr A. 2014 ; 1358: 68–74.