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High-performance liquid chromatographic method for the determination of atracurium and laudanosine in human plasma: Application to pharmacokinetics
Affiliation:1. Laboratoire de Pharmacocinétique Clinique, Faculté de Pharmacie, 34060 Montpellier Cedex 2, France;2. Laboratoire de Biophysique, Faculté de Pharmacie, 34060 Montpellier Cedex 2, France;3. Fédération d’Anesthésie Réanimation et de l’Urgence, Centre Hospitalier Universitaire, Nı̂mes Cedex, France;1. Department of Pharmaceutical Sciences, Università degli Studi di Milano, Via Giuseppe Colombo, 71, 20133 Milan, Italy;2. Italian Medicines Agency (AIFA), via del Tritone, 181, 00187 Rome, Italy;1. Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium;2. Hôpital Erasme-Gastroenterology, Université Libre de Bruxelles, Bruxelles, Belgium
Abstract:A high-performance liquid chromatographic method coupled with fluorimetric detection has been developed for the determination of atracurium and its major metabolite, laudanosine, in human plasma. The detection is performed at 240 nm for excitation and 320 nm for emission. Verapamil was used as the internal standard. The proposed technique, involving the direct precipitation of plasma proteins is reproducible, selective and sensitive. Linear detector responses were observed for the calibration curve standards in the range of 40 to 2000 ng/ml. Precision, expressed as C.V., was in the range 1 to 14%. The limit of quantification for both atracurium and laudanosine was 40 ng/ml. The method has been validated and stability tests under various conditions have been performed. This method has been used to determine the pharmacokinetic profile of atracurium and laudanosine in patients with acute respiratory distress syndrome.
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