The use of electron impact and positive chemical ionization mass spectrometry in the screening of beta blockers and their metabolites in human urine

Abstract

The use of several mass spectrometry technologies including electron impact (EI) and positive chemical ionization (CI) in both full-scan and multiple ion detection (MID) analysis for the urine analysis of several beta blockers and metabolites has been investigated. These drugs were extracted using an alkaline solid-phase extraction procedure and identified as their respective trimethylsilyl-trifluoroacetyl (TMS-TFA) derivatives on capillary gas chromatography/mass spectrometry. Isobutane proved to be the preferred reagent gas for the positive CI mass spectrometry of TMS-TFA derivatives of beta blockers, in comparison with others, such as methanol, ammonia and methane, since mass spectra with little fragmentation and abundant ions at high mass were obtained. By combining EI mass spectrometry and isobutane positive CI mass spectrometry using the ion trap detector, the identities of the main co-extracted metabolites were confirmed. Absolute detection limits were 0.15 ng for full-scan analysis (EI as well as positive CI mass spectrometry) and 0.08 ng for MID analysis (EI as well as CI mass spectrometry). The detection times of beta blockers in human urine were at least two- to three-fold the elimination half-life of these drugs. The analytical potential of the above mass spectrometric techniques has been discussed.

Rapid chiral separation of metoprolol in plasma—application to the pharmacokinetics/pharmacodynamics of metoprolol enantiomers in the conscious goat

“…5 ) by capilliary gas chromatography/mass spectrometry after solid-phase extraction and a trimethylsilylationtrifluoroacetylation derivatization reaction. Details ot this procedure have been published elsewhere (Leloux and Maes, 1990b). Our results have revealed that these three metabolites were formed irrespective of the stereochemical constitution of the beta-blocking drug infused.…”

Comparison of the analysis of β-blockers by different techniques

“…Most of the chromatographic methods are based on gas chromatography/mass spectrometry coupling (GC/MS), requiring the derivatization of polar groups (aminopropanol chain) of compounds [11,14,[17][18][19][21][22][23]25,26]. However, the GC-MS analysis of the most polar ␤-blockers appeared a real analytical, which has limited the use of this technique.…”

“…Different techniques have been used to determine ␤-blockers in urine, including methods based on spectrofluorimetry [6][7][8], ELISA [9,10], and chromatography [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Most of the chromatographic methods are based on gas chromatography/mass spectrometry coupling (GC/MS), requiring the derivatization of polar groups (aminopropanol chain) of compounds [11,14,[17][18][19][21][22][23]25,26].…”

In vivo biotransformation of metoprolol in the horse and on-column esterification of the aminocarboxylic acid metabolite by alcohols during solid phase extraction using mixed mode columns

“…Detection of metoprolol and its metabolites by capillary GC-mass spectrometry (GC/MS) as oxazolidinonetrimethylsilyl [11] perfluoroacyl [12] and mixed TFA-TMS [13] has been described. Metoprolol and its metabolites have also been analysed by high performance liquid chromatog- raphy (HPLC) with fluorescence detection [14,15].…”