Predictable Increase of Central Nervous System Stimulation by a Pyrolysis Product in Smoking Dimethylamphetamine

264 Journal of Health Science, 50(3) 264–270 (2004) Predictable Increase of Central Nervous System Stimulation by a Pyrolysis Product in Smoking Dimethylamphetamine Motoyasu Sato,*, a Kenjiro Ito,a and Hisamitsu Nagaseb aScientific Investigation Research Laboratory, Aichi Pref. Police H.Q., 2–1–1 Sannomaru, Naka-ku, Nagoya 460–8502, Japan and bGifu Pharmaceutical University, 5–6–1 Mitahora-higashi, Gifu 502–8585, Japan (Received January 10, 2004; Accepted February 6, 2004) We carried out a dimethylamphetamine (DMA) smoking experiment that is closer to some real cases. In this study, we heated DMA hydrochloride (DMA-HCl) in the range of about 250°C to 350°C, in which demethylation reaction occurred mainly, with a smoke collection apparatus and gas lighter, and trapped the generating vapor with an adsorption cartridge. The eluate desorbed from the cartridge and residual materials inside the smoke collection apparatus were analyzed by gas chromatography-mass spectrometry and liquid chromatography-electrospray ionization-mass spectrometry. Methamphetamine (MA) and amphetamine (AM) were produced via demethylation from the dimethylamino group of DMA. Allylbenzene (AB), benzaldehyde (BA), cis-β-methylstyrene (cMS), benzyl chloride (BC) and trans-β-methylstyrene (tMS) in addition to MA and AM, were also formed as pyrolysis products. The molar percentages of a pyrolyzate MA and AM to the starting DMA were 21.4 and 1.8%, respectively, and the total molar percentage of AB, BA, cMS, BC and tMS was 2.9%. Taking into account the central nervous system stimulation by DMA and MA in humans, the total stimulant effects of the drugs that are ingested in a body can be calculatedly increased more than fourfold by smoking DMA. The present data show that a DMA smoking abuser may be able to get a more powerful stimulant effect by smoking than by injecting. Key words —–— dimethylamphetamine, methamphetamine, amphetamine, pyrolysis product, smoking INTRODUCTION or similar device. Some abusers make use of a glass tube or a light bulb instead of aluminum foil. MA is Methamphetamine (MA) comprises a large pro- detected in urine as a metabolite after ingestion of portion of the drugs abused in Japan. MA is usually some other drugs.3–11) Dimethylamphetamine (DMA) self-administered through intravenous injection; is one of these drugs and is controlled in Japan. The however, it can be also smoked orally. When smoked, major excretion products of DMA in humans is MA is effectively absorbed, and it is this rapid in- dimethylamphetamine N-oxide, and MA and am- flux of the drug that produces effects similar to those phetamine (AM) are also excreted as minor metabo- produced after intravenous administration.1) In Ja- lites.6) There are several reports on the pyrolysis pan, MA smoking accounts for a majority of drug products of MA,12–14) while there is only our previ- use by minors.2) MA smoking lowers the resistance ous report regarding the pyrolysis products of to drug abuse because the abusers avoid a guilty feel- DMA.15) In recent years, DMA or DMA-MA mix- ing and a dark image, and do not feel the need to ture has been sold on the street and used as a stimu- worry about being arrested for injection marks on lant drug in Japan. DMA abusers believe that they the skin. Most smoking abusers place the drug on a are using just MA, not DMA, because the colorless piece of aluminum foil and inhale the vapors released crystals of DMA look just like those of MA-HCl. by heating it with a lighter-usually through a straw This situation makes us to predict that some abusers will smoke DMA like MA. Little is, however, known of the pharmacological effects by its pyrolyzates to *To whom correspondence should be addressed: Scientific In- vestigation Research Laboratory, Aichi Pref. Police H.Q., 2–1– which DMA smoking abusers are exposed. 1 Sannomaru, Naka-ku, Nagoya 460–8502, Japan. Tel.: +81- We already clarified several pyrolysis products, 52-951-1611 (ext. 4734); Fax: +81-52-951-1650; E-mail: sato- their formation temperatures and the pyrolysis [email protected] mechanisms of DMA-HCl.15) DMA-HCl was placed No. 3 265 in the sealed glass tube and heated at the Curie point Palo Alto, CA, U.S.A.) connected to a JMS-600W of a pyrolysis-foil wrapping around the sealed glass mass spectrometer (JEOL Ltd., Tokyo, Japan) using tube. The major pyrolysis process at below 358°C a CP-Sil 8CB column (50 m × 0.32 mm i.d., film was demethylation reaction from the dimethylamino thickness 5.0 µm, Chrompak, Middelburg, The Neth- group of DMA, which yielded MA and AM. The erlands). The column temperature was raised from demethylation reaction of the dimethylamino group 80°C to 230°C at 10°C/min, with a 1 min hold at occurred at above 255°C, and the formation ratio of 80°C and a 9 min hold at 230°C. Helium was used MA, a demethylated product of DMA, went up to as a carrier gas at a flow rate of 1.5 ml/min. The the maximum at 358°C. However, this experimen- injection port was used at splitless mode and main- tal condition will promote the pyrolysis by keeping tained at 240°C. Other operating conditions were as DMA and its pyrolyzates in sealed space without follows: electron ionization (EI), electron energy of vaporizing. It is difficult to directly apply these re- 70 eV, ion source temperature at 200°C, interface sults that were obtained in a sealed space to some temperature at 240°C, mass range of m/z 50 to 500. real cases of DMA smoking abusers. Thus we car- The quantitative analyses were carried out in selected ried out a DMA smoking experiment that is closer ion monitoring (SIM) mode using m/z 118 for mo- to some real cases. The vaporizing temperature of lecular ions (M+) of AB, cMS and tMS, m/z 106 for d-DMA-HCl was 194°C by measuring with thermo- M+ of BA, m/z 126 for M+ of BC and m/z 120 for M+ gravimetry. In this study, we heated DMA-HCl in of AP as internal standard (IS). the range of about 250°C to 350°C, in which LC-ESI-MS analyses were performed on an Al- demethylation reaction is a main pyrolysis pathway, liance 2690 HPLC (Waters Corp., Mass., U.S.A.) with a smoke collection apparatus and gas lighter, connected to a ZMD electrospray ionization mass and trapped the generating vapor with an adsorp- spectrometer (Micromass Ltd., Manchester, U.K.). tion cartridge. The eluate desorbed from the cartridge At the flow rate of 100 µl/min, 50% of acetonitrile and the residual materials inside the smoke collec- and 20 mM ammonium acetate buffer (pH 5) was tion apparatus were analyzed by gas chromatogra- passed through a Chiral DRUG column (150 mm × phy-mass spectrometry (GC-MS) and liquid chro- 2 mm i.d., Shiseido Ltd., Tokyo, Japan) with a 3 µm matography-electrospray ionization-mass spectrom- pre-filter (5 mm × 4 mm i.d.). In the previous re- etry (LC-ESI-MS). In this report, we will predict port, we clarified the formation of a quaternary am- what effects its pyrolyzate by smoking DMA has on monium, benzylethyltrimethylammonium, by heat- the pharmacological effects of DMA. ing DMA-HCl,15) and used the chiral column to get the quaternary ammonium detectable in this experiment. The ion source temperature, desolvation tem- MATERIALS AND METHODS perature, capillary voltage and cone voltage were kept at 100°C, 300°C, 3.0 kV and 30 V, respectively. Materials —–— d-Methamphetamine HCl The qualitative and quantitative analyses were car- (MA-HCl) was purchased from Dainippon Pharma- ried out in positive ion and full-scan modes in the ceutical Co. Ltd., (Osaka, Japan). d-Amphetamine mass range of m/z 50 to 400. The ions used for quan- 1/2H2SO4 (AM-1/2H2SO4) and d-dimethylamphet- titative analyses were m/z 136, 150 and 164, which amine HCl (DMA-HCl) were synthesized by the were protonated molecules [M+H]+ of AM, MA and method as described previously.15) Allylbenzene DMA, respectively. (AB), cis-β-methylstyrene (cMS) and trans-β- Calibration Curves —–— The methanol solution methylstyrene (tMS) were purchased from Tokyo containing AB, BA, cMS, BC and tMS was serially Kasei Kogyo Co., Ltd. (Tokyo, Japan); Acetophe- diluted with dichloromethane. To 1ml of the diluted none (AP), benzaldehyde (BA) and benzyl chloride solution containing 0.1, 0.5, 2, 5, 10 µg/ml of the (BC) from Wako Pure Chemical Industries, Ltd. five compounds, 50 µl of methanol solution contain- (Osaka, Japan). All other chemicals used were of ing 10.6 µg of AP as IS was added, and 1µl of the the highest purity available commercially. A mixed solutions were injected into GC-MS. The cali- Supelclean ENVI-Carb SPE cartridge (500 mg) was bration curves were prepared with the peak area ra- purchased from Supelco, Inc. (Bellefonte, PA, tios to IS. The calibration curves of AB, BA, cMS, U.S.A.). BC and tMS were all linear as follows. AB: y = Instrumentation —–— GC-MS analyses were car- –0.0076 + 0.1194X [0.1 – 10 µg/ml, r = 0.999], BA: ried out on an HP 6890 GC (Hewlett Packard Co., y = –0.0169 + 0.2177X [0.1 – 10 µg/ml, r = 0.999], 266 Vol. 50 (2004) cMS: y = –0.0018 + 0.1131X [0.1 – 10 µg/ml, r = 0.999], BC: y = –0.0004 + 0.1165X [0.1 – 10 µg/ml, r = 0.999], tMS: y = –0.0008 + 0.1125X [0.1 – 10 µg/ ml, r = 0.999].

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