Determination of modafinil in plasma and urine by reversed phase high-performance liquid-chromatography

Abstract

Modafinil (Provigil) is a new wake-promoting drug that is being used for the management of excessive sleepiness in patients with narcolepsy. It has pharmacological properties similar to that of amphetamine, but without some of the side effects associated with amphetamine-like stimulants. Since modafinil has the potential to be abused, accurate drug-screening methods are needed for its analysis. In this study, we developed a high-performance liquid-chromatographic procedure (HPLC) for the quantitative analysis of modafinil in plasma and urine. (Phenylthio)acetic acid was used as an internal standard for the analysis of both plasma and urine. Modafinil was extracted from urine and plasma with ethyl acetate and ethyl acetate-acetic acid (100:1, v/v), respectively, and analyzed on a C18 reverse phase column with methanol-water-acetic acid (500:500:1, v/v) as the mobile phase. Recoveries from urine and plasma were 80.0 and 98.9%, respectively and the limit of quantitation was 0.1 microg/mL at 233 nm. Forty-eight 2-h post-dose urine samples from sham controls and from individuals taking 200 or 400 mg of modafinil were analyzed without knowledge of drug administration. All 16-placebo urine samples and all 32 2-h post-dose urine samples were correctly classified. The analytical procedure is accurate and reproducible and can be used for therapeutic drug monitoring, pharmacokinetic studies, and drug abuse screening.

Effects of modafinil and methylphenidate on visual attention capacity: a TVA-based study

“…Modafinil in all samples was analysed using a modified high performance liquid chromatographic method with diode array detection (Schwertner and Kong 2005). Separation of modafinil and difluoro-modafinil (internal standard) was performed on a Symmetry C18 reversed phase column after sample preparation by liquid/liquid extraction.…”

Intrinsic Stability Study of Armodafinil Hydrochloride by Forced Degradation and Impurity Profiling

“…pharmacokinetics of adrafinil by liquid chromatography / tandem mass spectrometric (LC-MS / MS) method [2]; determination of AMD in human plasma [3] and in plasma and urine [4]; HPLC determination of AMD along with its synthetic intermediates [5,6]; capillary electrophoresis enantiomeric determination [7].…”

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

“…Since armodafinil is an isomer of modafinil, these methods might be applicable for the quantification of armodafinil as well. Several bioanalytical methods such as high-performance liquid chromatography (HPLC) coupled with photodiode array detector ( PDA) or ultraviolet detector (UV) detection, GC-MS and LC-MS/MS have been reported in the literature for the determination of modafinil and modafinil isomers (Burnat, Robles and Do 1998, Cass and Ferreira Galatti 2008, Dubey, Ahi, Reddy, Kaur, Beotra and Jain 2009, Harvanova and Gondova 2017, McKinney, Suann and Stenhouse 2005, Moachon and Matinier 1994, Schwertner and Kong 2005, Tseng, Uralets, Lin and Kuo 2005). However, all of these published methods require more than 100 μL of plasma volume makes it difficult sometimes in a patient population where multiple samples needed for therapeutic drug monitoring.…”