Chiral Analysis of Methamphetamine in Oral Fluid Samples: A Method to Distinguish Licit from Illicit Drug Use

Abstract

Methamphetamine (MAMP) is a popular illicit drug abused for its central nervous system stimulating effects. MAMP is also used therapeutically in the treatment of overeating disorders, narcolepsy, attention deficit disorder, in over-the-counter (OTC) products to ease nasal congestion. MAMP exists in two enantiomeric forms, dextrorotary (d-MAMP) or levorotary (l-MAMP). The compounds are similar in chemical structure, simply differing in the orientation of functional groups around the asymmetric carbon. In part because of the availability of l-MAMP in OTC nasal inhalers, forensic guidelines require a sample to contain greater than 20% d-MAMP to consider illicit drug use when interpreting results. Standard analytical methods readily detect MAMP in biological specimens but cannot resolve the enantiomeric composition of the sample. Specialized analytical techniques based on chiral separation of the enantiomers are required to differentiate d-MAMP from l-MAMP. Our laboratory sought to develop and validate a method for the analysis of oral fluid specimens for d/l-MAMP using a chiral derivatizing agent and traditional reverse phase liquid chromatography tandem mass spectrometry (LC-MS-MS). MAMP was extracted from dilute oral fluid samples using Strata-XC solid phase extraction (SPE) cartridges and derivatized with Marfey's reagent. Chromatographic separation was achieved using Zorbax Eclipse Plus C18 columns. Linearity, accuracy and precision, recovery, matrix effects and specificity of the method were all within acceptable criteria. Intraday accuracy ranged from 93.3 to 103.4% and precision 0.1 to 1.6%. Interday accuracy ranged from 90.0 to 103.4% and precision 3.8 to 11.6%. Finally, having previously tested positive for MAMP using non-chiral analysis, 256 de-identified authentic oral fluid samples were analyzed using this validated method. 98% of all samples tested positive for d-MAMP at greater than 20%.

Pharmacokinetics of selegiline, R‐methamphetamine, R‐amphetamine, and desmethylselegiline in oral fluid after a single oral administration of selegiline

“…That is, when a single oral dose of SG is taken, there is a period of time in OF in which only MA and AM are present without SG and DM‐SG. Thus, when differentiating clinical SG use from MA abuse, we cannot simply judge by the existence of SG or not but require chiral separation of MA and AM . Interestingly, SG was reported as a stimulant in one article .…”

“…24 SG was rapidly eliminated from OF with a t 1/2 value of approxi- from MA abuse, we cannot simply judge by the existence of SG or not but require chiral separation of MA and AM. 10,11 Interestingly, SG was reported as a stimulant in one article. 16 Considering the 50 mg/L initial screening cut-off concentration for AMP-type stimulants in OF, already proposed by US SAMHSA and by Standards Australia, 12,26 SG was detected in our study in 100%, 25%, and 0% of the OF specimens collected at 0.5 hours, 1 hour, and 2 hours, respectively.…”

“…The difference is mainly because the S‐form has a psychotonic activity 5‐fold stronger than the R‐form . It has been reported that the way to differentiate clinical SG use from MA abuse is chiral analysis of MA and AM in biological specimens, including oral fluid (OF) specimens …”

“…[7][8][9] It has been reported that the way to differentiate clinical SG use from MA abuse is chiral analysis of MA and AM in biological specimens, including oral fluid (OF) specimens. 6,8,10,11 OF has been successfully used as an alternative matrix for blood testing in several pharmacokinetic studies and pharmacotoxicological studies. 12 The pharmacokinetic data is meaningful for the results interpretation in forensic analysis.…”

Application of a chiral high‐performance liquid chromatography‐tandem mass spectrometry method for the determination of 13 related amphetamine‐type stimulants to forensic samples: Interpretative hypotheses

“…As stereocenters can be retained or sometimes formed during metabolic reactions, a characterization including the full stereochemistry facilitates the detection of hypothetical metabolic connections. Several analytical methods for the enantioselective analysis of amphetamine and methamphetamine (using different techniques and matrices) have been published recently 12,24–28 . However, a comprehensive method including potential metabolites of these compounds is lacking.…”