Jump to ContentJump to Main Navigation

Archives of Industrial Hygiene and Toxicology

The Journal of Institute for Medical Research and Occupational Health

4 Issues per year


IMPACT FACTOR increased in 2014: 0.932
5-year IMPACT FACTOR: 1.120

SCImago Journal Rank (SJR) 2014: 0.303
Source Normalized Impact per Paper (SNIP) 2014: 0.647
Impact per Publication (IPP) 2014: 1.017

Open Access
VolumeIssuePage

Issues

Determination of Benzodiazepines in Urine Via Benzophenone Derivatives Using Liquid Chromatography-Tandem Mass Spectrometry

Robert Roškar1 / Marija Dolenc1

Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia1

This content is open access.

Citation Information: Archives of Industrial Hygiene and Toxicology. Volume 61, Issue 4, Pages 381–388, ISSN (Print) 0004-1254, DOI: 10.2478/10004-1254-61-2010-2058, December 2010

Publication History

Published Online:
2010-12-23

Determination of Benzodiazepines in Urine Via Benzophenone Derivatives Using Liquid Chromatography-Tandem Mass Spectrometry

The aim of this study was to validate a new method for determining benzodiazepines in urine via their benzophenone derivatives, based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Selected benzodiazepines were analysed after acid hydrolysis of urine and extraction by ethyl acetate in the presence of an internal standard. Samples were analysed using electrospray ionization LC-MS/MS in a multiple reaction monitoring mode. The chromatographic run time on a reversed phase C18 analytical column was set for 9 min. This method was validated in 21 patients receiving methadone. Benzodiazepines intake was established in two out of three patients. LC-MS/MS results were also compared with the rapid immunoassay and the methods showed good agreement. However, in three cases benzodiazepines were detected by LC-MS/MS, but not by the immunoassay. The sensitivity of the developed LC-MS/MS method is comparable to or even higher than of previously reported methods, which makes it suitable as a confirmatory method.

Določanje benzodiazepinov v urinu preko benzofenonskih derivatov z uporabo tekočinske kromatografije sklopljene s tandemsko masno spektrometrijo

Razvili smo selektivno in občutljivo metodo za določanje nekaterih benzodiazepinov v urinu preko določanja njihovih benzofenonov. Metoda temelji na tekočinski kromatografiji, sklopljeni s tandemsko masno spektrometrijo (LC-MS/MS). Izbrane benzodiazepine smo analizirali po kisli hidrolizi urinskih vzorcev in ekstrakciji z etilacetatom v prisotnosti internega standarda. Vzorce smo analizirali z elektrorazprševalno ionizacijo z MRM načinom detekcije. Čas kromatografske ločbe na reverznofazni (C18) analitski koloni je bil 9 min.

Metoda je bila validirana in preizkušena na 21 pacientih, ki so prejemali metadonsko terapijo. Pri dveh tretjinah primerov je bil vnos benzodiazepinov tudi potrjen. Vzorce smo testirali tudi s hitro imunokemijsko metodo in rezultate primerjali z rezultati pridobljenimi z LC-MS/MS metodo. Ugotovili smo dobro ujemanje med rezultati pridobljenimi z obema metodama. Kljub temu smo v treh primerih določili prisotnost benzodiazepinov z LC-MS/MS metodo, ki je z imunokemijsko metodo nismo. Občutljivost razvite metode je primerljiva ali celo boljša od predhodno opisanih metod, zato jo lahko uporabimo kot potrditveno metodo.

Keywords: benzodiazepine metabolites; diazepam; drug abuse; lorazepam; methadone treatment

Keywords: diazepam; lorazepam; presnovki benzodiazepinov; metadonska terapija; zloraba zdravil

  • Lader M. Anxiolytic drugs: dependence, addiction and abuse. Eur Neuropsychopharmacol 1994;4:85-91.

  • Lavie E, Fatséas M, Denis C, Auriacombe M. Benzodiazepine use among opiate-dependent subjects in buprenorphine maintenance treatment: Correlates of use, abuse and dependence. Drug Alcohol Depend 2009;99:338-44. [Web of Science]

  • Barnas C, Rossmann M, Roessler H, Reimer Y, Fleischhacker WW. Benzodiazepines and other psychotropic-drugs abused by patients in a methadone-maintence program-familiarity and preference. J Clin Psychopharmacol 1992;12:397-402.

  • Bramness JG, Kornør H. Benzodiazepine prescription for patients in opioide maintence treatment in Norway. Drug Alcohol Depend 2007;90:203-9. [Web of Science]

  • Gambart D, Cárdenas S, Gallego M, Valcárcel M. An automated screening system for benzodiazepines in human urine. Anal Chim Acta 1998;366:93-102.

  • Cárdenas S, Gallego M, Valcárcel M. Gas chromatographicmass spectrometric confirmation of selected benzophenones from benzodiazepines in human urine following automatic screening. J Chromatogr A 1998;823:389-99.

  • Drummer OH. Methods for the measurement of benzodiazepines in biological samples. J Chromatogr B Biomed Sci Appl 1998;713:201-25.

  • Beck O, Lafolie P, Odelius G, Boreus LO. Immunological screening of benzodiazepines in urine: improved detection of oxazepam intake. Toxicol Lett 1990;52:7-14.

  • Violon C, Pessemier L, Vercruysse A. High-performance liquid chromatography of benzophenone derivates for the determination of benzodiazepines in clinical emergencies. J Chromatogr 1982;236:157-68.

  • Schutz H. Benzodiazepines: A Handbook. Heidelberg: Springer-Verlag; 1982.

  • Cheze M, Villain M, Pepin G. Determination of bromazepam, clonazepam and metabolites after a single intake in urine and hair by LC-MS/MS. Application to forensic cases of drug facilitated crimes. Forensic Sci Int 2004;145:123-30.

  • Borrey D, Meyer E, Lambert W, Van Peteghem C, De Leenheer AP. Simultaneous determination of fifteen lowdosed benzodiazepines in human urine by solid-phase extraction and gas chromatography-mass spectrometry. J Chromatogr B Biomed Sci Appl 2001;765:187-97.

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Núbia C. de Paula, Kelly C.F. Araujo Cordeiro, Paula L. de Melo Souza, Diogo F. Nogueira, Diego B. da Silva e Sousa, Maísa B. Costa, François Noël, and Valéria de Oliveira
Bioorganic & Medicinal Chemistry Letters, 2015, Volume 25, Number 5, Page 1026

Comments (0)

Please log in or register to comment.