Improved gas chromatographic method for the quantitation of plasma pethidine and norpethidine: application in determining pharmacokinetic parameters in Chinese patients after intramuscular administration of pethidine

Kelvin Chan, University of Wolverhampton, United Kingdom

Abstract

A sensitive and accurate gas liquid chromatographic (GLC) method is described to determine pethidine and norpethidine in plasma of Chinese patients who received a single dose (1 mg/kg of total body weight) of pethidine intramuscularly. The chromatograph consists of a 3% w/w SP2250 on Chromosorb W glass column linked to a nitrogen-phosphorus detector. Sample preparation was simple, being based on a single extraction of basified plasma samples with n-hexane. The operating time of the assay was less than thirty minutes, which was suitable for routine pharmacokinetic studies of both pethidine and norpethidine. This method was sensitive to 5 ng/ml of pethidine and 10 ng/ml of norpethidine extracted from 1 ml plasma sample. Linearity was observed in the range of 10 to 500 ng/ml. The day-to-day variation at the concentration of 100 ng/ml of pethidine and norpethidine was 3.3 and 4.27% respectively. The mean ( ± S.D.) peak plasma concentration, the mean ( ± S.D.) time for maximum absorption, and the mean ( ± S.D.) elimination half-life of pethidine was 246.4 ± 65.9 ng/ml, 0.75 ± 0.31 hr., and 7.95 ± 2.22 hrs respectively. The N-demethylated metabolite, norpethidine, appeared in the plasma from 0.5 to 1 hour and the mean ( ± S.D.) peak plasma concentration was 28.8 ± 4.38 ng/ml. The mean elimination half-life (39.6 ± 19.3 hrs) was significantly greater than pethidine.