Preparation of Deuterium-Labeled Armodafinil by Hydrogen–Deuterium Exchange and Its Application in Quantitative Analysis by LC-MS

<p>Armodafinil, the R enantiomer of modafinil, was approved in 2007 by the US Food and<br> Drug Administration as a wake-promoting agent for excessive sleepiness treatment. Due to its<br> abuse by students and athletes, there is a need of its quantification. Quantitative analysis by liquid<br> chromatography-mass spectrometry, however, though very common and sensitive, frequently cannot<br> be performed without isotopically labeled standards which usually have to be specially synthesized.<br> Here we reported our investigation on the preparation of deuterated standard of armodafinil based<br> on the simple and inexpensive hydrogen&ndash;deuterium exchange reaction at the carbon centers. The<br> obtained results clearly indicate the possibility of introduction of three deuterons into the armodafinil<br> molecule. The introduced deuterons do not undergo back exchange under neutral and acidic<br> conditions. Moreover, the deuterated and non-deuterated armodafinil isotopologues revealed coelution<br> during the chromatographic analysis. The ability to control the degree of deuteration using<br> different reaction conditions was determined. The proposed method of deuterated armodafinil<br> standard preparation is rapid, cost-efficient and may be successfully used in its quantitative analysis<br> by LC-MS.</p>