Simultaneous determination of nerisopam,a novel anxiolytic agent showing polymorphic metabolism,and its N-acetyl metabolite from human plasma by a validated high-performance liquid chromatographic method |
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| Affiliation: | 1. Haynal Imre University of Medical Sciences, Department of I. Medicine, P.O. Box 112, 1389 Budapest, Hungary;2. EGIS Pharmaceuticals Ltd., Department of Pharmacokinetics, P.O. Box 100, 1475 Budapest, Hungary;3. Institute for Drug Research, P.O. Box 82, 1325 Budapest, Hungary;1. Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands;2. Department of PharmacoTherapy, -Epidemiology and -Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands;3. Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands;4. Pharmaceutical Analysis, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands;1. Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Airforce Station, Palaj, Gandhinagar 382355, Gujarat, India;2. Department of Natural Products, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Airforce Station, Palaj, Gandhinagar 382355, Gujarat, India;1. Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576 104, Udupi, Karnataka, India;2. Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research, Hajipur, 844 102, Bihar, India |
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| Abstract: | A sensitive reversed-phase high-performance liquid chromatographic method with ultraviolet absorbance detection has been developed to simultaneously determine the concentrations of nerisopam (EGIS-6775) and its N-acetyl metabolite (EGIS-7649) from human plasma. The separation of the investigated compounds and internal standard was achieved on a Nucleosil 7 C18 column with 2 mM heptanesulphonic acid containing 0.04 M phosphoric acid-acetonitrile-methanol (70:25:5 v/v), pH 2.7 mobile phase. The detection was performed at 385 nm. The compounds were isolated from plasma by Bakerbond C18 solid-phase extraction. The limit of quantitation was 10 ng/ml plasma for each compound investigated. The assay has been validated with respect to accuracy, precision and system suitability. All validated parameters were found to be within the necessary limits. On the basis of the sensitivity, linearity and validation parameters, the developed analytical method was found to be suitable for the determination of nerisopam and its N-acetyl metabolite from human plasma and for application in pharmacokinetic studies and human drug monitoring. The pharmacokinetic parameters obtained from twelve human volunteers are reported. It was found that nerisopam acetylation is polymorphic: the volunteers with fast or slow acetylator phenotypes produced significantly different plasma concentrations. In slow acetylator phenotypes the concentration of nerisopam was considerably higher in plasma, while the level of its acetyl metabolite was higher in plasma of fast acetylators. |
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