ABSTRACT
BACKGROUND: A fast and sensitive assay for quantifying total and unbound concentrations of lorazepam (Lzp), oxazepam (Ozp) and temazepam (Tzp) in human plasma was needed for a plasma protein binding study. RESULTS: Plasma samples were precipitated with acetonitrile for determination of total concentrations or subjected to ultrafiltration for determination of unbound concentrations. An LC-MS/MS assay was developed with an Allure® PFP propyl column and a mobile phase of 35% acetonitrile/0.1% formic acid over 4.5 min and ESI+-MS/MS detection. Matrix effects were negligible in plasma and approximately 70% in ultrafiltrate but were accounted for by the internal standards Lzp-d4, Ozp-d5 and Tzp-d5. The assay was validated for total concentrations of 10-100 ng/ml Lzp, 200-2000 ng/ml Ozp and 100-1000 ng/ml Tzp, and for unbound concentrations of 1-10 ng/ml Lzp, 20-200 ng/ml Ozp and 10-100 ng/ml Tzp. Precision was <14% CV and accuracy was 96-110% throughout the calibration range. The mean precision of triplicate analysis of 60 study samples was <4% CV for total and <8% CV for unbound concentrations. CONCLUSION: A fast and sensitive assay was developed and validated. It has been applied successfully to a protein binding study.
Subject(s)
Anti-Anxiety Agents/blood , Lorazepam/blood , Oxazepam/blood , Temazepam/blood , Anti-Anxiety Agents/chemistry , Anti-Anxiety Agents/standards , Calibration , Chromatography, Liquid , Hemofiltration , Humans , Lorazepam/chemistry , Lorazepam/standards , Oxazepam/chemistry , Oxazepam/standards , Tandem Mass Spectrometry , Temazepam/chemistry , Temazepam/standardsSubject(s)
Aviation/standards , Fatigue/prevention & control , Hypnotics and Sedatives/pharmacokinetics , Temazepam/pharmacokinetics , Chemistry, Pharmaceutical , Humans , Hypnotics and Sedatives/standards , Occupational Health/legislation & jurisprudence , Temazepam/standards , Work Schedule ToleranceSubject(s)
Benzodiazepines/metabolism , Escherichia coli/enzymology , Glucuronidase/metabolism , Lorazepam/analogs & derivatives , Lorazepam/metabolism , Oxazepam/analogs & derivatives , Oxazepam/metabolism , Temazepam/analogs & derivatives , Temazepam/metabolism , Humans , Hydrolysis , Immunoassay , Lorazepam/standards , Oxazepam/standards , Temazepam/standardsABSTRACT
The goal of this study was to focus on the adoption process for a specific new drug upon its introduction to the marketplace. The reception of temazepam by doctors was investigated in interviews with 124 specialists and general practitioners. Their response to this new drug at different stages of the adoption process was related to contact with drug information sources and to characteristics of the doctor and practice. Within about 13 months after its release, 71% were familiar with temazepam, 48% had prescribed it, and 27% now preferred it to the alternatives. Contact with the detailman regarding this drug was the most consistent predictor of favourable reception. Results suggest that the adoption of the new drug was related to commercial forces rather than to a doctor's professional involvements.
