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 wwere 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.

A Pharmacokinetic Approach to Postoperative Pain: Continuous Infusion of Pethidine

“…Single intramuscular injections of pethidine produce blood concentrations which increase to a maximum within one hour and decrease in an exponential manner. However, rates of absorption of pethidine after intramuscular injections vary and result in a wide range of maximum concentrations and considerable variation in the times at which these occur (Chan, Kendall and Mitchard 1974, Chan et al 1975, Hartvig et al 1977, Mat'her et al 1975, Shih, Robinson and Au 1976, Stambaugh and Wainer 1974, Stambaugh et al 1976. Little is known about therapeutic blood levels of pethidine although plasma concentrations of 0.2 p,g/ml were analgesic in 8 young women following abdominal tuballigations (Shih et al 1976).…”

Pharmacokinetics of Pethidine During Anaesthesia and Patient‐Controlled Analgesic Therapy

“…Blood samples were collected throughout the period of self-administration. The plasma concentrations of pethidine and norpethidine were determined by electron capture gas chromatography after selective isolation and derivatization ( HARTVIG et al 1977). Plasma protein binding of pethidine was determined by equilibrium dialysis (SJOHOLM et al 1976).…”

Patient-controlled Analgesic Therapy, Part I

“…The pethidine concentration in plasma and haemolysed whole blood was assayed by gas chromatography with electron capture detection (Hartvig et al, 1976(Hartvig et al, , 1977. Concentrations are expressed as total plasma concentrations of pethidine base.…”