Adrafinil

Adrafinil (CRL-40028, Olmifon), prodrug of modafinil, is a mild central nervous system stimulant drug used to relieve excessive sleepiness and inattention, Adrafinil is believed to serve as an alpha-1 adrenoceptor agonist.

A novel study of screening and confirmation of modafinil, adrafinil and their metabolite modafinilic acid under EI-GC-MS and ESI-LC-MS-MS ionization.[Pubmed:20407560]

Indian J Pharmacol. 2009 Dec;41(6):278-83.

OBJECTIVE: Adrafinil and modafinil have received wide publicity and have become controversial in the sporting world when several athletes were discovered allegedly using these drugs as doping agents. By acknowledging the facts, the World Anti-Doping Agency (WADA) banned these drugs in sports since 2004. The present study explores the possibility of differentiating Adrafinil and modafinil and their major metabolites under electron impact ionization in gas chromatograph-mass spectrometer (GC-MSD) and electrospray ionization in liquid chromatograph-mass spectrometer (LC-MS/MS) by studying the fragmentation pattern of these drugs. MATERIALS AND METHODS: Adrafinil, modafinil and their major metabolite, modafinilic acid were analyzed on EI-GC-MSD and ESI-LC-MS/MS using various individual parameters on both the instruments. The analytical technique and equipment used in the analysis were an Agilent 6890N GC with 5973 mass selective detector for the GC-MSD analysis and an Agilent 1100 HPLC with API-3200 Triple quadrupole mass spectrometer for the LC-MS/MS analysis. Validation of both methods was performed using six replicates at different concentrations. RESULT AND DISCUSSION: The results show that Adrafinil, modafinil and their major metabolite modafinilic acid could be detected as a single artifact without differentiation under EI-GC-MSD analysis. However, all drugs could be detected and differentiated under ESI-LCMS/MS analysis without any artifaction. The GC-MSD analysis gives a single artifact for both the drugs without differentiation and thus can be used as a marker for screening purposes. Further, the Multiple Reaction Monitoring (MRM) method developed under LC-MS/MS is fit for the purpose for confirmation of suspicious samples in routine sports testing and in forensic and clinical analysis.

Development of a validated LC method for enantiomeric separation and determination of adrafinil and its related substances on a Chiralcel OJ-H column connected to PDA and polarimetric detectors in series.[Pubmed:20954215]

Biomed Chromatogr. 2010 Nov;24(11):1228-33.

A rapid and reliable high-performance liquid chromatographic method for resolution of enantiomers of Adrafinil [(+/-)-ADL], a novel vigilance promoting agent, and its synthetic intermediates was developed. The separation was carried out on a Chiralcel OJ-H using n-hexane-ethanol (62:38 v/v) as a mobile phase. The detection was carried out at 225 nm using a photodiode array (PDA) detector. The optical rotation and order of elution of enantiomers were assigned. The method is suitable not only for process development of ADL but also for quality assurance of bulk drugs and pharmaceuticals.

Fluorescent zinc and copper complexes for detection of adrafinil in paper-based microfluidic devices.[Pubmed:27293080]

Chem Commun (Camb). 2016 Jul 7;52(53):8279-82.

Recognition of electroneutral Lewis bases and anions in aqueous media is extremely difficult. We show that fluorescent coordinatively unsaturated metal complexes can recognize various Lewis bases while providing an easy-to-detect fluorescence response. This approach is applied to the detection of Adrafinil, a banned performance-enhancing drug.

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.[Pubmed:27928893]

Drug Test Anal. 2017 Mar;9(3):518-528.

2-[(Diphenylmethyl)sulfinyl]acetamide (modafinil) is commonly prescribed for the treatment of narcolepsy. Increasing popularity and off-label use as a cognitive enhancer has 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, and 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 (1) H and (13) C 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 analogue 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 analogues. These observations served as a reminder that the seemingly straightforward implementation of GC-MS analysis can lead to challenges during routine analysis.