title: Determination of buprenorphine, norbuprenorphine and naloxone in fingernail clippings and urine of patients under opioid substitution therapy.
abstract: The aim of this study was to develop and validate a method for the determination of buprenorphine (BUP), norbuprenorphine (NBUP) and naloxone (NAL) in fingernails and urine samples collected from former heroin users under suboxone substitution therapy. The analytes were extracted by solid-liquid or solid-phase extraction and were analyzed by liquid chromatography-mass spectrometry. The validation of the analytical methods developed included linearity, recovery, accuracy, precision, ion suppression, sensitivity of interfaces and limits of determination and quantification. The validated methods were applied to samples from 46 individuals. The majority of the urine samples were positive for all analytes (93.5% for BUP, 95.7% for NBUP and 84.8% for NAL). In nails, a higher detection rate was observed for NBUP and BUP (89.1%), compared with NAL (10.9%). The median values of the NBUP/BUP and the NAL/BUP ratio were 2.5 and 0.3 in urine and 0.8 and 0.3 in nails, respectively. A statistically significant correlation was found between the BUP, NBUP and total BUP (BUP and NBUP) concentrations in urine and those in nails. A weak correlation was observed between the daily dose (mg/day) and total BUP (P = 0.069), or NBUP (P = 0.072) concentrations in urine. In contrast, a strong correlation was found between the total amount of BUP administered during the last 12 months and total BUP (P = 0.038), or NBUP (P = 0.023) concentrations in urine. Moreover urine BUP, NBUP and total BUP concentrations correlated significantly. Our study demonstrated successfully the application of the developed method for the determination of the three analytes in urine and nails.
authors: Department of Toxicology and Forensic Science, School of Medicine, University of Crete, Heraklion, Greece.
authors: Manolis N
authors: MN
authors: Tzatzarakis
authors: Department of Toxicology and Forensic Science, School of Medicine, University of Crete, Heraklion, Greece.
authors: Elena
authors: E
authors: Vakonaki
authors: Laboratory of Forensic Medicine and Toxicology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors: Leda
authors: L
authors: Kovatsi
authors: Department of Toxicology and Forensic Science, School of Medicine, University of Crete, Heraklion, Greece.
authors: Stamatis
authors: S
authors: Belivanis
authors: Greek National Organization Against Drugs, Athens, Greece.
authors: Mary
authors: M
authors: Mantsi
authors: Department of Toxicology and Forensic Science, School of Medicine, University of Crete, Heraklion, Greece.
authors: Athanasios
authors: A
authors: Alegakis
authors: Department of Pharmacology, Drug Development and Therapeutics, Institute of Biomedicine, University of Turku, Turku, Finland.
authors: Jyrki
authors: J
authors: Liesivuori
authors: Department of Toxicology and Forensic Science, School of Medicine, University of Crete, Heraklion, Greece aris@med.uoc.gr.
authors: Aristidis M
authors: AM
authors: Tsatsakis
mesh_terms: D000328:Adult; D002047:Buprenorphine / Q000031:analogs & derivatives* / Q000032:analysis / Q000652:urine; D000069479:Buprenorphine, Naloxone Drug Combination / Q000627:therapeutic use; D002853:Chromatography, Liquid; D005260:Female; D006556:Heroin Dependence / Q000534:rehabilitation* / Q000652:urine; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D009262:Nails / Q000737:chemistry*; D009270:Naloxone / Q000032:analysis / Q000652:urine*; D009292:Narcotic Antagonists / Q000627:therapeutic use; D058850:Opiate Substitution Treatment; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction
chemical_list: D000069479:Buprenorphine, Naloxone Drug Combination; D009292:Narcotic Antagonists; D009270:Naloxone; D002047:Buprenorphine; C043585:norbuprenorphine