Simultaneous chiral impurity analysis of methamphetamine and its precursors by supercritical fluid chromatography–tandem mass spectrometry
Impurity profiling of seized illicit methamphetamine (MA) provides information on MA manufacturing methods in clandestine laboratories, and this drug intelligence supports formulation of strategies to control MA abuse. In the present study, we developed a simultaneous chiral analysis method for MA and its precursors using supercritical fluid chromatography–tandem mass spectrometry equipped with an enantioselective stationary phase.
Chromatographic conditions were optimized by systematic investigation of the flow rate, temperature, back pressure, co-solvent, additive, and mobile phase composition. The ability of the developed method was evaluated using standard and authentic illicit MA.
The use of a chiral selector in the stationary phase allowed for simultaneous chiral differentiation of MA and its precursors including ephedrine, norephedrine, chloropseudoephedrine, methylephedrine, dimethylamphetamine, and amphetamine. Sufficient limit of detection, repeatability of retention time, and linearity were achieved. A switching valve interfacing a chromatograph and a mass spectrometer enabled analyzing large amounts of MA directly. The application to the authentic illicit MA samples was achieved and revealed the existence of impurities, which was not detected by conventional gas chromatography–mass spectrometry.
The developed supercritical fluid chromatography–tandem mass spectrometry method could be a powerful analytical tool for MA impurity profiling.
KeywordsMethamphetamine Supercritical fluid chromatography Mass spectrometry Impurity profiling
This study was supported by Brandenberger–Matsumoto Award 2018 from the Japanese Association of Forensic Toxicology, and the content will be presented at The International Association of Forensic Toxicologist 2018 meeting in Ghent, Belgium. This study was also supported in part by the Japan Society for the Promotion of Science KAKENHI Grant-in Aid for Young Scientists (B) (Grant Number JP17K12994). We thank Gabrielle David, PhD from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies involving human participants or animals performed by any of the authors.
- 1.United nations office on drugs and crime, word drug report 2018. Available at: https://www.unodc.org/wdr2018/ Accessed 27 Jun 2018
- 4.Stojanovska N, Fu S, Tahtouh M, Kelly T, Beavis A, Kirkbride KP (2013) A review of impurity profiling and synthetic route of manufacture of methylamphetamine, 3,4-methylenedioxymethylamphetamine, amphetamine, dimethylamphetamine and p-methoxyamphetamine. Forensic Sci Int 224:8–26. https://doi.org/10.1016/j.forsciint.2012.10.040 CrossRefGoogle Scholar
- 7.Remberg B, Stead A (1999) Drug characterization/impurity profiling, with special focus on methamphetamine: recent work of the United Nations International Drug Control Programme. Bull Narc 51:97–117Google Scholar
- 9.Qi Y, Evans I, McCluskey A (2007) New impurity profiles of recent Australian imported ‘ice’: methamphetamine impurity profiling and the identification of (pseudo)ephedrine and Leuckart specific marker compounds. Forensic Sci Int 169:173–180. https://doi.org/10.1016/j.forsciint.2006.08.016 CrossRefGoogle Scholar
- 10.Toske SG, McConnell JB, Brown JL, Tuten JM, Miller EE, Phillips MZ, Vazquez ER, Lurie IS, Hays PA, Guest EM (2015) Isolation and characterization of a newly identified impurity in methamphetamine synthesized via reductive amination of 1-phenyl-2-propanone (P2P) made from phenylacetic acid/lead (II) acetate. Drug Test Anal 9:453–461. https://doi.org/10.1002/dta.1814 CrossRefGoogle Scholar
- 11.Puthaviriyakorn V, Siriviriyasomboon N, Phorachata J, Pan-ox W, Sasaki T, Tanaka K (2002) Identification of impurities and statistical classification of methamphetamine tablets (Ya-Ba) seized in Thailand. Forensic Sci Int 126:105–113. https://doi.org/10.1016/S0379-0738(02)00018-X CrossRefGoogle Scholar
- 14.Iwata YT, Inoue H, Kuwayama K, Kanamori T, Tsujikawa K, Miyaguchi H, Kishi T (2006) Forensic application of chiral separation of amphetamine-type stimulants to impurity analysis of seized methamphetamine by capillary electrophoresis. Forensic Sci Int 161:92–96. https://doi.org/10.1016/j.forsciint.2006.01.018 CrossRefGoogle Scholar
- 15.Iwata YT, Kanamori T, Ohmae Y, Tsujikawa K, Inoue H, Kishi T (2003) Chiral analysis of amphetamine-type stimulants using reversed-polarity capillary electrophoresis/positive ion electrospray ionization tandem mass spectrometry. Electrophoresis 24:1770–1776. https://doi.org/10.1002/elps.200305431 CrossRefGoogle Scholar
- 16.Liau A-S, Liu J-T, Lin L-C, Chiu Y-C, Shu Y-R, Tsai C-C, Lin C-H (2003) Optimization of a simple method for the chiral separation of methamphetamine and related compounds in clandestine tablets and urine samples by β-cyclodextrine modified capillary electrophoresis: a complementary method to GC–MS. Forensic Sci Int 134:17–24. https://doi.org/10.1016/S0379-0738(03)00096-3 CrossRefGoogle Scholar
- 17.Tagliaro F, Manetto G, Bellini S, Scarcella D, Smith FP, Marigo M (1998) Simultaneous chiral separation of 3,4-methylenedioxymethamphetamine (MDMA), 3-4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxyethylamphetamine (MDE), ephedrine, amphetamine and methamphetamine by capillary electrophoresis in uncoated and coated capillaries with native β-cyclodextrin as the chiral selector: preliminary application to the analysis of urine and hair. Electrophoresis 19:42–50. https://doi.org/10.1002/elps.1150190109 CrossRefGoogle Scholar
- 19.Hensley D, Cody JT (1999) Simultaneous determination of amphetamine, methamphetamine, methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), and methylenedioxyethylamphetamine (MDEA) enantiomers by GC-MS. J Anal Toxicol 23:518–523. https://doi.org/10.1093/jat/23.6.518 CrossRefGoogle Scholar
- 21.LeBelle MJ, Savard C, Dawson BA, Black DB, Katyal LK, Zrcek F, By AW (1995) Chiral identification and determination of ephedrine, pseudoephedrine, methamphetamine and metecathinone by gas chromatography and nuclear magnetic resonance. Forensic Sci Int 71:215–223. https://doi.org/10.1016/0379-0738(94)01669-0 CrossRefGoogle Scholar
- 25.Toribio L, Bernal JL, Martín MT, Bernal J, Nozal MJ (2014) Effects of organic modifier and temperature on the enantiomeric separation of several azole drugs using supercritical fluid chromatography and the Chiralpak AD column. Biomed Chromatogr 28:152–158. https://doi.org/10.1002/bmc.3013 CrossRefGoogle Scholar