Forensic Science International xxx (2008) xxx–xxx j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / f o r s c i i n t Sildenafil analogs used for adulterating marihuana MSn revealed the presence of a carbohydrate in sample A and thepresence of two illegal analogs of sildenafil (Viagra1) in Sample B(). The illegal erectogenics were identified as a mixture ofthio-homosildenafil (THS) and its chemical precursor homosilde- nafil (HS) in a 10:1 ratio, using a method described by our laboratory earlier In addition, traces of several related chemical structures were detected but these were not identified further. Reference standards had been isolated from adulterated dietary supplements in previous investigations .
A crude smoking experiment confirmed that THS, HS and reference sildenafil citrate could be inhaled by smoking. For thisexperiment, a portion of Sample B was evaporated leaving awhite powder. Cigarettes were prepared using 1.2 g of hand-rolling tobacco to which was added the arbitrary amount of 15 mg of sildenafil citrate or THS/HS powder. Cigarettes weremounted on a gas-washing bottle filled with 300 ml of MeOH In recent years marihuana was found adulterated with and a gentle vacuum was applied allowing the cigarette to burn powdered glass or chalk The adulterants adhered to the at a rate of approximately 1 cm/min. After the cigarette had naturally excreted resin making it the marihuana look like being of burned for 5 min, the MeOH solution was analyzed by HPLC– a higher quality. Earlier this year in Germany elemental lead had been used as an adulterant to increase weight, causing symptoms 475 ! 377; HS: m/z 489 ! 461 and THS m/z 505 ! 355) of poisoning in at least 100 marihuana smokers Because of the For chromatographic separation 5 ml was injected on a Waters health risk adulterants may pose marihuana is regularly checked in Symmetry C18 column (2.1 mm  100 mm, 3.1 mm) held at 30 8C The Netherlands for the presence of adulterants.
using Solvent A—0.1% (v/v) formic acid in ACN and Solvent B— We report here a case study where two liquids used for 0.1% (v/v) formic acid in H2O: 0–20 min gradient elution from A/ adulterating marihuana were investigated for the presence of B = 5/95 to 90/10, 20–25 min isocratic A/B = 90/10, 25–30 min: adulterants. Samples A and B were provided to our laboratory in plastic screw-capped container and without any further descrip- Both THS and HS are phosphodiesterase 5 (PDE-5) inhibitors tion. Standard analysis using HPLC–DAD-MSn and direct infusion like sildenafil (Viagra1) and so far were identified in illegal Fig. 1. UV chromatogram of the suspicious liquid with homosildenafil (RT = 6.07) and thio-homosildenafil (RT = 23.95). The grey areas indicate the differences in chemicalstructure from sildenafil.
0379-0738/$ – see front matter ß 2008 Elsevier Ireland Ltd. All rights reserved.
doi: Please cite this article in press as: B.J. Venhuis, D. de Kaste, Sildenafil analogs used for adulterating marihuana, Forensic Sci. Int. (2008),doi: / Forensic Science International xxx (2008) xxx–xxx erectogenics only. The effect a PDE-5 inhibitor would exert on lung [4] F. Busse, L. Omidi, A. Leichtle, M. Windgassen, E. Kluge, M. Stumvoll, Lead poisoning due to adulterated marijuana, N. Engl. J. Med. 358 (2008) tissue is well described in literature. In patients suffering from pulmonary hypertension orally administered sildenafil (Revatio1) [5] L. Blok-Tip, B. Zomer, F. Bakker, K.D. Hartog, M. Hamzink, J. Ten Hove, M.
causes pulmonary vasodilatation improving their breathing .
Vredenbregt, D. De Kaste, Structure elucidation of sildenafil analogues in herbalproducts, Food Addit. Contam. 21 (2004) 737–748.
No reports on smoking of PDE-5 inhibitors could be found in [6] B.J. Venhuis, G. Zomer, D. de Kaste, Structure elucidation of a novel synthetic literature, but inhalation of nebulized sildenafil is reportedly thiono analogue of sildenafil detected in an alleged herbal aphrodisiac, J. Pharm.
Assuming marihuana is adulterated with PDE-5 inhibitors for a [7] N.B. Charan, Does sildenafil also improve breathing? Chest 120 (2001) 305–306.
[8] M. Guazzi, G. Tumminello, F. Di Marco, M.D. Guazzi, Influences of sildenafil on specific reason the adulterators may aim at evoking drug–drug lung function and hemodynamics in patients with chronic heart failure, Clin.
interactions. Though interactions studies were not found in Pharmacol. Ther. 76 (2004) 371–378.
literature a recent US study showed a strong association between [9] M. Guazzi, G. Tumminello, F. Di Marco, C. Fiorentini, M.D. Guazzi, The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and males smoking marijuana and taking un-prescribed sildenafil diffusion capacity, exercise ventilatory efficiency, and oxygen uptake kinetics in tablets The investigators suggest sildenafil may be used to chronic heart failure, J. Am. Coll. Cardiol. 44 (2004) 2339–2348.
counter marijuana-induced loss of libido. Still, in our case, this [10] F. Ichinose, J. Erana-Garcia, J. Hromi, Y. Raveh, R. Jones, L. Krim, M.W. Clark, J.D.
Winkler, K.D. Bloch, W.M. Zapol, Nebulized sildenafil is a selective pulmonary does provide a solid rationale for smoking marihuana with a PDE- vasodilator in lambs with acute pulmonary hypertension, Crit. Care Med. 29 5 inhibitor unless the objective is to keep buyers unaware.
As this is the first and only case there is the possibility of an [11] M.C. Aubin, S. Laurendeau, A. Mommerot, Y. Lamarche, A. Denault, M. Carrier, L.P.
Perrault, Differential effects of inhaled and intravenous sildenafil in the preven- isolated incident. However, since PDE-5 inhibitor could have an tion of the pulmonary endothelial dysfunction due to cardiopulmonary bypass, J.
effect it may still be not coincidental. A possible explanation that Cardiovasc. Pharmacol. 51 (2008) 11–17.
should be investigated is whether an interaction could arise [12] M.L. Eloi-Stiven, N. Channaveeraiah, P.J. Christos, M. Finkel, R. Reddy, Does marijuana use play a role in the recreational use of sildenafil? J. Fam. Pract. 56 resulting in the increased uptake of psychoactive components from marihuana smoke, enhancing the experience. Such a study wouldcontribute to the understanding and health risks of the con-comitant use of marihuana and PDE-5 inhibitors.
RIVM - National Institute for Public Health and the Environment, P.O. Box 1, NL-3720BA Bilthoven, The Netherlands [1] M. McBride, Government report: seizures of cannabis contaminated with glass particles, Department of Health, Social Services and Public Safety, *Corresponding author. Tel.: +31 30 274222; [2] M. McBride, Government report: update on seizures of cannabis contaminated with glass particles, Department of Health, Social Services and Public Safety, [3] J.G.C. van Amsterdam, J. van Marle, P. van Dijk, R. Niesink, A. Opperhuizen, Govern- ment report: electronmicroscopic investigations of contaminated samples of marijuana (report in Dutch), National Institute for Public Health and the Environ-ment, Please cite this article in press as: B.J. Venhuis, D. de Kaste, Sildenafil analogs used for adulterating marihuana, Forensic Sci. Int. (2008),doi:


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