Generic sample preparation combined with high-resolution liquid chromatography- time-of-flight mass spectrometry for unification of urine screening in doping-control laboratories

R.J.B. Peters, J.E. Oosterink, A.A.M. Stolker, C.G. Georgakopoulos, M.W.F. Nielen

Research output: Contribution to journalArticleAcademicpeer-review

44 Citations (Scopus)

Abstract

A unification of doping-control screening procedures of prohibited small molecule substances—including stimulants, narcotics, steroids, ß2-agonists and diuretics—is highly urgent in order to free resources for new classes such as banned proteins. Conceptually this may be achieved by the use of a combination of one gas chromatography–time-of-flight mass spectrometry method and one liquid chromatography–time-of-flight mass spectrometry method. In this work a quantitative screening method using high-resolution liquid chromatography in combination with accurate-mass time-of-flight mass spectrometry was developed and validated for determination of glucocorticosteroids, ß2-agonists, thiazide diuretics, and narcotics and stimulants in urine. To enable the simultaneous isolation of all the compounds of interest and the necessary purification of the resulting extracts, a generic extraction and hydrolysis procedure was combined with a solid-phase extraction modified for these groups of compounds. All 56 compounds are determined using positive electrospray ionisation with the exception of the thiazide diuretics for which the best sensitivity was obtained by using negative electrospray ionisation. The results show that, with the exception of clenhexyl, procaterol, and reproterol, all compounds can be detected below the respective minimum required performance level and the results for linearity, repeatability, within-lab reproducibility, and accuracy show that the method can be used for quantitative screening. If qualitative screening is sufficient the instrumental analysis may be limited to positive ionisation, because all analytes including the thiazides can be detected at the respective minimum required levels in the positive mode. The results show that the application of accurate-mass time-of-flight mass spectrometry in combination with generic extraction and purification procedures is suitable for unification and expansion of the window of screening methods of doping laboratories. Moreover, the full-scan accurate-mass data sets obtained still allow retrospective examination for emerging doping agents, without re-analyzing the samples.
Original languageEnglish
Pages (from-to)2583-2598
JournalAnalytical and Bioanalytical Chemistry
Volume396
Issue number7
DOIs
Publication statusPublished - 2010

Keywords

  • solid-phase extraction
  • veterinary drugs
  • high-throughput
  • masking agents
  • uplc-tof
  • diuretics
  • stimulants
  • glucocorticosteroids
  • beta(2)-agonists
  • corticosteroids

Fingerprint Dive into the research topics of 'Generic sample preparation combined with high-resolution liquid chromatography- time-of-flight mass spectrometry for unification of urine screening in doping-control laboratories'. Together they form a unique fingerprint.

Cite this