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??L of plasma for the analysis. The chromatographic separation was performed with a Waters symmetry, C18 , 4.6?×?150?mm, 5??m 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.

SUBMITTER: Chandasana H 

PROVIDER: S-EPMC6191358 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature