Simultaneous determination of therapeutic plasma concentrations of pethidine and norpethidine in man by electron capture gas chromatography

Abstract

An analytical procedure for the simultaneous determination of pethidine and its N-Demethylated metabolite, norpethidine, in plasma is described. Pethidine and norpethidine are separated by partition chromatography, converted to the trichloroethyl carbamate with trichloroethyl chloroformate and determined by electron capture gas chromatography. The smallest amounts of pethidine and norpethidine determined by the method were 10 and 2 ng, respectively, in 0.1 ml plasma. The relative standard deviation in the determination of 50 ng of pethidine and 40 ng of norpethidine in 0.1 ml plasma were 5.8% (n=8) and 6.3% (n=10), respectively. The method was used to determine plasma levels of pethidine and norpethidine in three patients who received subcutaneous doses of pethidine 50–75 mg for postoperative pain. The peak levels of pethidine were found to be in the range 200–400 ng/ml, with a plasma half-life of the order of 4 hours. The levels of norpethidine were low.