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Outsmarted by nooptropics? An investigation into the thermal degradation of modafinil, modafinic acid, adrafinil, CRL-40,940 and CRL-40,941 in the GC injector: formation of 1,1,2,2-tetraphenylethane and its tetra fluoro analog.

Dowling, G and Kavanagh, PV and Talbot, B and O’Brien, J and Hessman, G and McLaughlin, G and Twamley, B and Brandt, SD (2017) Outsmarted by nooptropics? An investigation into the thermal degradation of modafinil, modafinic acid, adrafinil, CRL-40,940 and CRL-40,941 in the GC injector: formation of 1,1,2,2-tetraphenylethane and its tetra fluoro analog. Drug Testing and Analysis, 9 (3). pp. 518-528. ISSN 1942-7611

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Abstract

2-[(Diphenylmethyl)sulfinyl]acetamide (modafinil) is commonly prescribed for the treatment of narcolepsy and increasing popularity and off-label use as a cognitive enhancer resulted in a reputation as an intelligence boosting ‘wonder drug’. Common alternatives available from online shops and other retail outlets include 2-[(diphenylmethyl)sulfinyl]-N-hydroxyacetamide (adrafinil), 2-{[bis(4- fluorophenyl)methyl]sulfinyl}acetamide (CRL-40,940), 2-{[bis(4- fluorophenyl)methyl]sulfinyl}-N-hydroxyacetamide (CRL-40,941) and N-methyl-4,4-difluoro-modafinil (modafiendz), respectively. Gas chromatography mass spectrometry (GC-MS) is a common tool used in forensic and clinical analysis but there is a potential for inducing analysis-related ambiguities. This study reports on the thermal degradation of modafinil, modafinic acid, adrafinil, CRL-40,940 and CRL- 40,941 due to exposure to the heated GC injection port dissolved in a variety of solvents. Key degradation products common to modafinil, modafinic acid, adrafinil analysis included diphenylmethanol and 1,1,2,2-tetraphenylethane (TPE), the latter of which was verified by its synthesis and characterization by x-ray crystallography. The investigated compounds were also characterized by 1H and 13C NMR. Diphenylmethane and thiobenzophenone were also identified in some instances. TPE formation was suggested to involve the generation of a benzhydrylium ion and its reaction with the sulfoxide oxygen of the parent compound to give an oxysulfonium intermediate. Correspondingly, the fluorinated TPE analog was formed during heat-induced degradation of modafiendz, CRL-40,940 and CRL-40,941, respectively. When a mixture of modafinil (non-fluorinated) and modafiendz (fluorinated) were subjected to GC analysis, 4,4'-(2,2-diphenylethane-1,1-diyl)bis(fluorobenzene) was detected as a third cross reaction product in addition to the two expected TPE analogs. These observations served as a reminder that the seemingly straightforward implementation of GC-MS analysis can lead to challenges during routine analysis.

Item Type: Article
Additional Information: This is the accepted version of the following article:Dowling, G., Kavanagh, P. V., Talbot, B., O’Brien, J., Hessman, G., McLaughlin, G., Twamley, B., and Brandt, S. D. (2017) Outsmarted by nootropics? An investigation into the thermal degradation of modafinil, modafinic acid, adrafinil, CRL-40,940 and CRL-40,941 in the GC injector: formation of 1,1,2,2-tetraphenylethane and its tetra fluoro analog. Drug Test. Analysis, 9: 518–528. doi: 10.1002/dta.2142, which has been published in final form at http://dx.doi.org/10.1002/dta.2142
Uncontrolled Keywords: 0301 Analytical Chemistry, 1115 Pharmacology And Pharmaceutical Sciences
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Wiley
Date Deposited: 06 Dec 2016 10:41
Last Modified: 22 Jun 2017 11:04
DOI or Identification number: 10.1002/dta.2142
URI: http://researchonline.ljmu.ac.uk/id/eprint/5004

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