Analytical and Bioanalytical Chemistry

, Volume 400, Issue 1, pp 17–23

Rapid quantification of tilidine, nortilidine, and bisnortilidine in urine by automated online SPE-LC-MS/MS

  • Christoph Köhler
  • Thomas Grobosch
  • Torsten Binscheck
Original Paper

DOI: 10.1007/s00216-010-4466-1

Cite this article as:
Köhler, C., Grobosch, T. & Binscheck, T. Anal Bioanal Chem (2011) 400: 17. doi:10.1007/s00216-010-4466-1

Abstract

The opioid tilidine is a prodrug which is hepatically metabolized to active nortilidine and bisnortilidine. Due to the increasing abuse of tilidine by drug users and the lack of a specific immunoassay, we developed an analytical method for the quantification of tilidine, nortilidine, and bisnortilidine in urine suitable for screening. In a following step, this method was used to establish data on excretion kinetics of the substances in order to evaluate the time window of detection after a single oral dose of tilidine/naloxone and also was applied to authentic urine samples from correctional facilities. Urine samples were mixed with internal standard solution and extracted on a weak cation exchanger at pH 6 using a Symbiosis Pico system. The chromatographic separation was achieved within a 3.5-min run time on a Phenylhexyl column (50 × 2.0 mm, 5 μm) via gradient elution (methanol and 0.2% formic acid) at a flow rate of 0.50 mL/min. The ESI-MS/MS was performed on a QTrap 3,200 in positive multiple reaction monitoring mode using two mass transitions per analyte. Validating the method resulted in a lower limit of quantification of 1.0 μg/L followed by a linear calibration range to 100 μg/L for each analyte (r2 > 0.99). The analytical method allowed the detection of a single dose of a commercially available tilidine solution up to 7 days after administration. Using this highly sensitive method, 55 of 3,665 urine samples were tested positive.

Keywords

TilidineNortilidineBisnortilidineOnline SPELC-MS/MS

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Christoph Köhler
    • 1
  • Thomas Grobosch
    • 1
  • Torsten Binscheck
    • 1
  1. 1.Institute of Toxicology–Clinical Toxicology and Poison Information CentreBerlinGermany