Determination of acamprosate in human plasma by UPLC-MS/MS: Application to therapeutic drug monitoring.

Acamprosate is a medication used to treat alcohol dependence. Therapeutic drug monitoring is important in drugs for the treatment of substance-related disorders. Therefore, in this study, a new selective, very simple and rapid ultra-performance liquid chromatography-tandem mass spectrometer method was developed for the therapeutic drug monitoring of acamprosate. The developed method allows the determination of acamprosate in human plasma. The method was validated in terms of selectivity and linearity, which was in the range of 100-1,200 ng/ml for acamprosate. Intra-assay and inter-assay accuracy and precision were within the acceptable limits of the Eueopean Medicines Agency guideline. The lower limit of quantitation was 100 ng/ml for acamprosate. The developed method was successfully applied for therapeutic drug monitoring in patient plasma samples.

Therapeutic Drug Monitoring of Naltrexone and 6ß-Naltrexol During Anti-craving Treatment in Alcohol Dependence: Reference Ranges.

AIMS: Aim of this study was to associate concentration of naltrexone and its major active metabolite 6ß-naltrexol in blood with therapeutic outcome during treatment with naltrexone in subjects with alcohol dependence. Treatment with the µ-opiate receptor antagonist naltrexone has been shown to reduce craving for alcohol and alcohol intake in patients suffering from alcohol dependence. SHORT SUMMARY: This article shows the use of therapeutic drug monitoring in alcohol dependent patients, who are treated with naltrexone. The plasma concentrations of naltrexone and 6ß-naltrexol showed high inter-individual variability. They were predictive for treatment response, as they correlated significantly with the reduction of alcohol craving. METHODS: Naltrexone and 6ß-naltrexol were analysed by high performance liquid chromatography with column switching and spectrophotometric detection. Alcohol craving was assessed with the Obsessive-Compulsive Drinking Scale (OCDS). RESULTS AND CONCLUSIONS: The study included 43 patients who were treated with naltrexone with a dose of 50 mg/day. Blood was taken for drug analysis 8 h after the last dose of the day at Week 4, 8 and 12. The plasma concentrations of naltrexone and 6ß-naltrexol showed high inter-individual variability. They were predictive for treatment response, as they correlated significantly with the reduction of alcohol craving. Defining patients with OCDS reduction of 70% or higher as responders, the mean±SD concentration of naltrexone plus naltrexol was 22 ± 13 ng/ml compared to 15 ± 8 ng/ml in patients with score reductions of 1-69%. Further analyses indicated that concentrations of 17-50 ng/ml at 8 h and 7-20 ng/ml at 24 h after drug intake were required for treatment response. CONCLUSIONS: Since plasma concentration of naltrexone plus 6ß-naltrexol was found to be predictive for reduction of alcohol craving, it is concluded that therapeutic drug monitoring has the potential to enhance naltrexone's moderate therapeutic efficiency in patients with alcohol dependence.