Quantitative determination of armodafinil in human plasma by liquid chromatography-electrospray mass spectrometry: Application to a clinical study.

Abstract

Armodafinil is a wake-promoting agent approved in 2007 by the US Food and Drug Administration for the treatment of excessive sleepiness. A rapid, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of armodafinil in human plasma was developed and validated. Armodafinil and internal standard (armodafinil d-10) were extracted from human plasma using protein precipitation combined with liquid-liquid extraction. This developed method only requires 50 μL of plasma for the analysis. The chromatographic separation was performed with a Waters symmetry, C18 , 4.6 × 150 mm, 5 μm column using formic acid, water and acetonitrile as solvent delivered at a 0.7 mL/min flow rate. The total run time of the method was 3 min. The method was validated according to regulatory guidance in terms of specificity, selectivity, linearity, matrix effect, recovery and stability. Optimized Q1/Q3 mass transitions for armodafinil and armodafinil d-10 were 274.1/167.2 (m/z) and 284.4/177.4 (m/z) respectively. The method showed linearity within the tested concentration range of 10-10,000 ng/mL. The method was successfully applied to quantify armodafinil concentrations after single oral administration of a 250 mg tablet in a clinical study conducted in healthy volunteers. Significant advantages of this method are minimal sample volume, short run time and a lower LLOQ.

• Authors: Hardik Chandasana, Johannes Kast, Janina A Bittman, Hartmut Derendorf
• Journal: Biomedical chromatography : BMC (Biomed Chromatogr) Vol. 32 Issue 11 Pg. e4342 (Nov 2018) ISSN: 1099-0801 [Electronic] England
• PMID: 30003558 (Publication Type: Journal Article)
• Copyright: © 2018 John Wiley & Sons, Ltd.

Chemical References

• Benzhydryl Compounds
• Modafinil

Topics

• Benzhydryl Compounds (blood, chemistry, pharmacokinetics)
• Chromatography, Liquid (methods)
• Drug Stability
• Humans
• Linear Models
• Modafinil
• Reproducibility of Results
• Sensitivity and Specificity
• Spectrometry, Mass, Electrospray Ionization (methods)
• Tandem Mass Spectrometry (methods)