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Abstract

A new simple and sensitive liquid chromatographyelectrospray ionization-tandem-mass spectrometric (LC-ESI-MS/MS) technique was developed and validated for the estimation of modafinil in human plasma and the method was applied to study pharmacokinetics in healthy rabbits. Chromatography was attained on Phenomenex-C 18 (50mm × 4mm) 5µ column and acetonitrile, methanol and 0.1% formic acid (25:60:15 v/v) mixture as the movable phase at 0.7 ml/min flowrate. Modafinil and modafinil-D5 internal standards were detected at m/z 274.2/229.0, m/z 279.1/234.0 respectively. Modafinil and modafinil-D5 (internal standard) were separated with liquid-liquid extraction. The technique was linear over the 2.0-600.0 ng/ml concentration range. This technique established with intrabatch and inter batch precision within 1.54-7.18% and 1.82-6.25%. This technique established with intrabatch and inter batch accuracy within 98.56-102.80% and 97.62-102.76 %.The drug was shown mean T max of 3.833; average C max, AUC0͢ t and AUC0͢ α , for test formulation is 677.667; 6306 and 6471 respectively in the pharmacokinetic study on healthy rabbits. INTRODUCTION: Modafinil acts as a eugeroic for the treatment of narcolepsy (sleepiness), sleep disorder due to different shift work and more daytime sleepiness which was associated with OPA (obstructive sleep apnea) 1-4. It was administered by the oral route. It acts by inhibiting selectively and weakly the dopamine reuptake process and indirectly promotes the releasing of histamines and orexin neurological peptides from the tuberomammillary nucleus and lateral hypothalamus, respectively and leads to contribution to heightened-arousal.