Drug-Drug Interactions of Heroin

Alcohol Many heroin users use heroin and alcohol together. There has been an evaluation of the pharmacokinetic interaction between heroin and alcohol and the role of that interaction in the cause of 39 heroin-related deaths that were attributed to either heroin or heroin + ethanol. The cases were arbitrarily divided into two groups according to blood ethanol concentration (low-ethanol group, under 1000 ng/ml, and high ethanol group, over 1000 μg/ml. The high-ethanol group was associated with reduced hydrolysis of 6-acetylmorphine to morphine, and there was an inverse correlation between blood ethanol concentration and hydrolysis of 6-acetylmorphine to morphine. The concentration of total morphine was lower in the high-ethanol group. High blood ethanol concentrations were also associated with an increased ratio of unbound to total morphine and with reduced excretion of unbound and total morphine. The relative concentrations of conjugated heroin metabolites were reduced in the presence of a high blood ethanol concentration. The authors hypothesized that alcohol inhibits the glucuronidation of morphine, resulting in less conjugated morphine in the blood. Thus, in patients with high blood ethanol concentrations the additional Read more […]

Immunoassay Detection of Benzodiazepines

Benzodiazepines were first introduced in the 1960s as a safer alternative to phenobarbital. In the 1970s and mid-1980s, diazepam (Valium) was the most commonly prescribed benzodiazepine. The dose levels and excretion patterns of these first generation benzodiazepines produced concentrations in samples that made drug detection easy by immunoassay. As chemists explored structure-activity relationships of this new class of compounds, a new generation of benzodiazepines was developed that exploited substituent activation of 1,4-benzodiazepine. These new benzodiazepines were more potent; therefore, they were prescribed in lower doses. This new generation of benzodiazepines was also fast acting and had much shorter half-lives with respect to blood concentrations and excretion levels. The higher doses and longer half-lives of the diazepam-related benzodiazepines, made it possible to detect this class of drugs by immunoassay screening. After a single dose of 5 mg of Valium, immunoassay detection is possible for up to 2 wk. With the lower dose, faster clearing benzodiazepines, (alprazolam, triazolam, lorazepam, nitrazepam, flunitrazepam, and clonazepam), detection by immunoassay at historical cutoff levels was nearly impossible. Read more […]

Immunoassay of Benzodiazepines

The following is an overview of the performance of the most widely used immunoassay screening methods and the effect of hydrolysis on the sensitivity of the methods. There are several widely marketed commercial products available to screen for benzodiazepmes. Most techniques cannot reliably detect therapeutic doses of the new generation of benzodiazepmes. The difference in performance between methods is mainly due to the different calibrators used and the difference in antibody cross-reactivities. The cross-reactivity is related to the antibody’s immunoreactivity to the parent drug of each analyte as well as each metabolite present. It is important to remember that quantitative results must be interpreted with caution, as the calibrator may be a different drug than the analyte(s) detected. Table Immunoassay Sensitivity and Cutoff Immunoassay LOD Cutoff FPIA 40 ng/mL 200 ng/mL EMIT 70 ng/mL 300 ng/mL CEDIA 6.8 ng/mL 200 ng/mL CEDIA 8.3 ng/mL 300 ng/mL OnLine 5 ng/mL 100 ng/mL SBENZ 7 ng/mL 7 ng/mL The role of the calibrator on the performance of the method is related to both the cutoff and the characteristic binding curve of the analyte chosen for the calibrator. Read more […]

Immunoassay of Benzodiazepines: Methods

Manual β-Glucuronidase Treatment The following procedure describes the manual glucuronidase treatment of a urine sample for the detection of benzodiazepines. The resultant hydrolyzed mixture can be applied to any standard analyzer and evaluated by the FPIA, EMIT, CEDIA, or OnLine methods. β-Glucuronidase (β-D-glucuronide glucuronosohydrolase, EC from E. coli can be obtained from Roche. It is available as a 50% glycerol-water solution and is used without any additional treatment. To a 1000-μL urine sample, add 50 μL of a 2 M phosphate buffer solution, pH 6.0, and vortex-mix thoroughly. To a 200-μL aliquot of the buffered urine sample, add 4 U of the enzyme preparation. (This should result in less than a 1.1 -fold dilution.) Incubate the mixture at ambient temperature for 30 min. Load the hydrolysate as sample into the system for analysis. Calibrators and controls should be treated in the same manner as the sample for consistency and to account for procedural variations. Lowering the cutoff of the immunochemical method, closer to the limit of detection, will further increase the clinical sensitivity. Automated β-Glucuronidase Treatment Toxicologists have adapted the enzyme hydrolysis procedure Read more […]