New article about Dibutylone
About Dibutylone. The structures of the hydrochloride hydrates of pentylone and dibutylone and the hydrochloride salt of ephylone, three new clandestinely-manufactured designer cathinones are described. Pentylone is (±)-1-(1,3-benzodioxol-5-yl)-2-(methylamino)pentan-1-one, dibutylone is (±)-1-(1,3-benzodioxol-5-yl)-2-(dimethylamino)butan-1-one, and ephylone is (±)-1-(1,3-benzodioxol-5-yl)-2-(ethylamino)pentan-1-one. These three drugs have recently appeared in law enforcement seizures of illicit drug materials and are referred to as NPS (new psychoactive substances). The free base pentylone crystallizes as the hydrochloride monohydrate salt with H bonds extending from the protonated amine to the Cl− anion very close to a center of symmetry, thence to a water of hydration, resulting in an interesting six-sided species of approximately chair conformation whose components are linked by hydrogen bonds. An interesting feature of the dibutylone free base is that it crystallizes as the HCl sesquihydrate salt. Most of the street drugs crystallize as their hydrates; but, unlike most of them, dibutylone HCl. 1.5H2O crystallizes as a kryptoracemate in space group P212121. A kryptoracemic crystal is one whose asymmetric unit contains a racemic pair, but still belongs in a Sohncke space group. The phenomenon was recognized relatively recently and, to date, there are very few drugs identified as crystallizing thus (for more on this topic, see below). In this structure, both independent amine cations have a chloride counter-anion, and they share three water molecules of crystallization, with the chloride anions and the waters forming an interesting H-bonded cyclic array. The free base ephylone crystallizes as the HCl salt and is a brand new substance, not appearing until about November 2015. The packing of all three of these cathinones contains “sandwich” π-π stacking interactions where the phenyl rings of the cations are stacked face-to-face with each other, with distances ranging from 3.531 to 3.862 Å. These compounds are among the most recent examples of cathinone-based stimulants designed to circumvent existing drug laws, and they represent a new danger to recreational drug users.
Dibutylone confirmation and quantitation
NMS Labs (Willow Grove, PA, USA) provided discarded postmortem blood (n = 9), urine (n = 4), vitreous humor (n = 1) and liver (n = 1) specimens from death investigation toxicology casework (n = 9) that had previously tested positive for dibutylone. Specimens were collected between January 2016 and July 2017. Personal identifiers were removed from any specimens or case histories before being provided. Case circumstances, when available, were tabulated and are provided in Table I (Case 1–9). Specimens were extracted using solid phase extraction (Agilent Bond Elut Plexa PXC, 3 mL, 30 mg). The extraction cartridges were conditioned with acetonitrile and water, the sample was applied and washed with hydrochloric acid in water (0.1 N) and acetonitrile, and the sample was eluted using a mixture of water, acetonitrile and ammonium hydroxide (55:40:5, v-v:v).
Table I.Case information for biological specimens and quantitative confirmation
Case Age Sex Case History Dibutylone Concentration (ng/mL) Butylone Concentration (ng/mL) Other Findings (ng/mL unless otherwise noted)
1 32 F Individual found deceased in bed; drug overdose suspected.
Femoral Blood: 383
Vitreous Humor: 250
Femoral Blood: 92.5
Vitreous Humor: 108
Femoral Blood: THC (2.8), THC-COOH (11)
2 46 M Individual found deceased in hotel room.
Femoral Blood: <10
Femoral Blood: 385
Femoral Blood: Alprazolam (110), Benzoylecgonine (1, 600), Hydrocodone (400), Oxycodone (13), Tramadol (340)
3 38 M Individual involved in fatal motor vehicle crash.
Femoral Blood: 61.5
Femoral Blood: 6.55Urine: 149
Femoral Blood: Ethanol (190 mg/dL), 4-Fluoroamphetamine, Methylone (31), Dimethylone, Ethylone (<10)
Urine: Ethylone (269)
4 – F Suspected drug overdose Femoral Blood: 1,400 Femoral Blood: 600 –
5 49 M Suspected use of “bath salts” Femoral Blood: 10 ND Femoral Blood: 4-Chloro-alpha-PVP
6 – M Unknown Central Blood: 11 ND –
7 – M Unknown Femoral Blood: 13 Blood: 12 –
8 – M Alleged “molly” use Postmortem Blooda: 14 ND –
9 – F Suspected drug overdose Postmortem Blooda: 40 Postmortem Blood: 15.3 Postmortem Blood: Para-fluoroisobutyrylfentanyl
10 37 M Sample collected at an electronic dance music festival. History of recreational drug use. Indicated use of “MDMA.” Took three (3) capsules within 24 hours of samples collection. Oral Fluid: 123.2 Oral Fluid: 206.2 Oral Fluid: Dimethylone, MDMA, MDA
11 22 M Sample collected at an electronic dance music festival. History of recreational drug use. Indicated use of “MDMA.” Took two (2) capsules within 24 hours of samples collection. Oral Fluid:137.6 Oral Fluid:291.3 Oral Fluid: Dimethylone, MDMA, MDA
12 – – Sample collected at an electronic dance music festival. Additional information unknown. Oral Fluid:1926.2 Oral Fluid:1761.4 Oral Fluid: Dimethylone, MDMA, MDA
13 29 M Sample collected at an electronic dance music festival. No indication of stimulant use. Oral Fluid: Positive Oral Fluid: Positive –
14 18 F Sample collected at an electronic dance music festival. History of recreational drug use. Took two (2) “Molly” within 24 hours of samples collection. Oral Fluid: Positive Oral Fluid: Positive –
15 26 M Sample collected at an electronic dance music festival. Additional information unknown. Oral Fluid: Positive Oral Fluid: Positive Oral Fluid: Cocaine