Observations on Methamphetamine Enantiomers

Abstract

Methamphetamine is a commonly used illegal drug and the use of the d form of methamphetamine (MAMP) can have serious implications for a patient’s treatment. Thus, correct identification of d methamphetamine is critical when releasing methamphetamine results although most reported positives are the result of illicit use, a small but significant number of MAMP positive findings can be from the use of medications that either contain or can be metabolized to MAMP. Neither common immunoassay screens nor routine mass spectral confirmatory methods can distinguish between the two forms of the drug because both forms have the same elemental composition and only differ in their orientation at the drug’s asymmetric carbon. Chromatographic chiral analysis which is a separation technique based upon the asymmetric carbon is used to resolve the drug into its enantiomeric forms. Historically, the test to differentiate the enantiomers has been time consuming requiring derivatization of the MAMP and a separate analytical system. The advent of newer chiral columns eliminates the need for derivatization and makes the analytical process simpler to automate. Federal workplace drug testing programs have established a threshold of 20% d-MAMP to distinguish between the legal and illegal use. The purpose of this study was to characterize positive MAMP results in the population of our test patients using both the derivatized and non-derivatized analytical procedures. The test population consisted of specimens collected from pain clinics and rehabilitation facilities. Of the 252,800 specimens tested between 3/28/16 and 2/3/17, we observed 11,264 specimens above our lower limit of quantitation of 50 ng/ml for methamphetamine. The average MAMP concentration was 32,530 ng/mL, while the median concentration was 27,882 ng/mL. There were 198 specimens in with 20% to 60% of the d enantiomer while 142 specimens contained greater than 99% of the l isomer. The average concentration of the d isomer value was 2074 ng/mL. The median concentration of the l isomer specimens was 166 ng/mL. However, 5 of these specimens contained MAMP concentrations greater than 20,000 ng/mL. Both methods of isomer analysis gave similar results with the d isomer measured to being 99% or greater in purity.