title: Determination of naltrexone and 6-beta-naltrexol in human plasma following implantation of naltrexone pellets using gas chromatography-mass spectrometry.
abstract: An alternative to detoxification by oral therapy with the narcotic antagonist naltrexone is the subcutaneous implantation of naltrexone pellets. From detoxified patients with naltrexone implants (1g) 26 blood samples were collected up to 73 days after implantation. The assay for naltrexone and 6-beta-naltrexol in plasma was developed using automated mixed-mode solid-phase extraction, catalysed trimethylsilylation and gas chromatography-mass spectrometry in single ion monitoring mode with naloxone as internal standard. The analytical method was very sensitive with limits of detection of 0.1 ng/ml and was linear up to 60 ng/ml for naltrexone and 200 ng/ml for naltrexol. Intra-day precision for naltrexone and naltrexol were 24.3 and 22.9%, respectively, at the LLOQ (accuracy 1.4 and 0.4%, respectively) and less than 10% (2.0, 6.0 and 20.0 ng/ml, n = 6 each) above. Inter-day precision was 7.9% (accuracy -0.6%) for naltrexone and 10.9% (accuracy 1.6%) for naltrexol (20 ng/ml, n = 10). Extraction recoveries were 83% for both analytes (10 ng/ml, n = 6). The concentrations of naltrexone and naltrexol in the plasma samples were in the range of 0.7-13.7 and 0.9-17.0 ng/ml, respectively. The simple analytical procedure described provided good sensitivity for the assay of naltrexone and naltrexol in plasma after naltrexone pellet implantation.
authors.affiliation: Center of Legal Medicine, Institute of Forensic Toxicology, University of Frankfurt, Kennedyallee 104, D-60596 Frankfurt/Main, Germany. toennes@em.uni-frankfurt.de
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Toennes
authors.forename: Gerold F
authors.initials: GF
authors.lastname: Kauert
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Grüsser
authors.forename: Werner
authors.initials: W
authors.lastname: Jäkel
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Partecke
mesh_terms: D004343:Drug Implants; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D015394:Molecular Structure; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D004343:Drug Implants; C010410:6 beta-hydroxynaltrexone; D009271:Naltrexone