Effects of buprenorphine in heroin addicts.

Twelve heroin addicts on the 8th day after withdrawal, and 8 healthy volunteers were given a single i.m. injection of buprenorphine 0.6 mg and their subjective response rated on 10 psychological variables. Pre-injection rating differed significantly between addicts and controls on 7 variables out of 10. Following buprenorphine more subjective changes were noted in the control group which became more calm, depressed, more aware of the environment, sleepy, tired, intoxicated, dizzy and nauseated. The drug addicts reported changes only in 2 variables (less tense and dysphoric) but otherwise showed no significant changes. These findings support the notion that buprenorphine induces low or normalizing effects in heroin addicts. This drug might thus be suitable for maintenance therapy in opiate addiction.

Analysis of buprenorphine and its N-dealkylated metabolite in plasma and urine by selected-ion monitoring.

A selected-ion monitoring method was developed for determination of buprenorphine and its N-dealkylated metabolite (norbuprenorphine) in human plasma and urine. N-Propylnorbuprenorphine was added as internal standard to 2-3 ml of sample and the alkaloids were extracted with toluene-2 butanol at pH 9.4. After back-extraction in dilute sulphuric acid, the compounds were heated at 110 degrees C. This procedure led to quantitative loss of methanol followed by ring formation between the 6-methoxy group and the branched side-chain of all compounds. The derivatives were extracted into dichloromethane-2-butanol and treated with pentafluoropropionic anhydride. The resulting derivatives were suitable for selected-ion monitoring analysis. The coefficient of variation was found to be 4.5% at 5 ng/ml and 8.9% at 50 ng/ml in urine. The corresponding values for plasma were 6.2% and 5.3%, respectively. The lower limit of detection in plasma was 150 pg/ml, permitting analysis of plasma levels of buprenorphine for 24 h and urine levels of buprenorphine and norbuprenorphine for more than seven days after a therapeutic dose of buprenorphine. This method is the first with sufficient specificity and sensitivity for characterization of the clinical pharmacokinetics of buprenorphine.

Determination of morphine in biological samples by gas chromatography-mass spectrometry. Evidence for persistent tissue binding in rats twenty-two days post-withdrawal.

Combined gas chromatography-mass spectrometry with capillary and packed column gas chromatography and a deuterium-labelled internal standard was used to determine morphine in biological specimens from rats 22 days after abrupt withdrawal. Morphine was extracted from urine and body organs at pH 9 and the pentafluoropropionyl derivatives were made for analysis by gas chromatography-mass spectrometry. The stationary phase was OV-17 and the mass spectrometer was focused on m/z 414 for morphine and m/z 417 for the internal standard, [NC2H3]morphine. With fused-silica capillary columns, the sensitivity of the assay was increased about ten-fold over packed columns. Urinary excretion of total morphine (free + conjugated) was 22 ng/h (range 11-51 ng/h, n = 8) at 22 days post-withdrawal. Free morphine was mainly detected in the lung (1.8-6.5 ng/g, n = 7), kidney (1.5-4.0 ng/g, n = 7) and liver (1.8-4.6 ng/g, n = 4). Traces of morphine were also detected in brain of some rats. Treatment with the opiate antagonist naltrexone, 10 mg/kg on four consecutive days before death, failed to change the urinary excretion pattern or the concentration of free morphine in body organs. The biological significance of the residual morphine, if any, remains to be determined.