DETERMINATION OF THE NOVEL NONSTEROIDAL ANTIINFLAMMATORY DRUG LORNOXICAM AND ITS MAIN METABOLITE IN PLASMA AND SYNOVIAL-FLUID

A rapid and sensitive HPLC method for the determination of the non-ste roidal anti-inflammatory drug lornoxicam in plasma samples of humans a nd laboratory animals is described. After addition of the internal sta ndard (tenoxicam) the plasma sample is acidified and extracted either by dichloromethane via Extrelut columns or by solid-phase extraction u sing C-18 columns. After evaporation of the solvent the separation is performed on a C-18 column in isocratic mode with a mobile phase consi sting of 0.1 M phosphate buffer (pH 6.0)-methanol and detection at 372 nm. The limit of determination was set to 10 ng/ml using 0.5 ml of sa mple but can be extended down to 2.0 ng/ml plasma. Using solid-phase e xtraction with C-18 columns both lornoxicam and its main metabolite 5' -hydroxylornoxicam can be determined while extraction via Extrelut was used in studies where only lornoxicam was to be determined. This meth od was used successfully in several thousand samples of pharmacokineti c and bioavailability studies in animals and in humans. (C) 1998 Elsev ier Science B.V.