Gas--liquid chromatographic evaluation of lofemizole in biological samples for pharmacokinetic investigations. Comparison of two analytical methods

The present paper reports the analytical conditions allowing lofemizole, a new non-steroidal anti-inflammatory drug, to be evaluated in biological fluids for pharmacokinetic and bioavailability investigations. The first approach led to an N-methyl derivative of lofemizole which could be successfully analysed by gas--chromatography employing a flame-ionization detector, reaching a sensitivity of 2 micrograms/ml. The second approach led to the N-(2-chlorobenzoyl) derivative of lofemizole which was suitable for pharmacokinetic investigation using gas--liquid chromatography with electron-capture detection, and reaching a much higher sensitivity of 10 ng/ml of plasma. Recovery of the extraction, reproducibility and specificity were all satisfactory with both methods. Since the first method employing flame-ionization detection was suitable for pharmacokinetic investigations in animal species, this paper describes both methods on a comparative basis.