High-performance liquid chromatographic method for the determination of atracurium and laudanosine in human plasma - Application to pharmacokinetics

A high-performance liquid chromatographic method coupled with fluorimetric detection has been developed for the determination of atracurium and its ma jor metabolite, laudanosine, in human plasma. The detection is performed at 240 nm for excitation and 320 nm for emission. Verapamil was used as the i nternal standard. The proposed technique, involving the direct precipitatio n of plasma proteins is reproducible, selective and sensitive. Linear detec tor responses were observed for the calibration curve standards in the rang e 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 con ditions have been performed. This method has been used to determine the pha rmacokinetic profile of atracurium and laudanosine in patients with acute r espiratory distress syndrome. (C) 1999 Elsevier Science B.V. All rights res erved.