High‐temperature ultra‐performance liquid chromatography coupled to hybrid quadrupole time‐of‐flight mass spectrometry applied to ibuprofen metabolites in human urine

Abstract

The application of sub-2 microm porous particle liquid chromatography (LC) operated at elevated temperatures, coupled with time-of-flight mass spectrometry (MS), to the separation and identification of metabolites of ibuprofen present in human urine following oral administrations is illustrated. The LC/MS system generated a high-resolution analytical separation that, with an analysis time of 20 min, provided a peak capacity in the order of ca. 350. Using this system a total of nine glucuronides of the drug and its metabolites were detected, including a number of isomeric acyl glucuronides of ibuprofen itself, a side-chain-oxidized carboxylic acid acyl glucuronide and a number of acyl glucuronides of various hydroxylated metabolites. The identities of the metabolites were confirmed by their accurate mass values and the presence of the common fragment ions from ibuprofen.

An approach towards method development for untargeted urinary metabolite profiling in metabonomic research using UPLC/QToF MS

“…Analytical conditions including the column [12], temperature [13], rapid gradients [14] have been tested, as well as the influence of sample separation techniques [15] and sample storage time [9] on urinary metabolite profiles. In the present study, we have compared various LC conditions and sample pre-treatments in order to further optimise the methodology for untargeted metabolite profiling.…”

Metabolism of the c-Fos/Activator Protein-1 Inhibitor T-5224 by Multiple Human UDP-Glucuronosyltransferase Isoforms

“…Fenselau and Johnson (1980) and Niemeijer et al (1991) reported that the O bond to the aromatic ring is not readily broken in the mass spectrometric analysis of phenols or phenol derivatives. The m/z 193 ion is considered to be the deprotonated glucuronic acid ion produced by cleaving the carboxyl group C-O bond, as reported by Jaggi et al (2002) and Plumb et al (2007) on the acyl O-glucuronides of desmethylnaproxen and ibuprofen. Given the mass spectrometric analysis and the fact that G2 is alkali-labile, this strongly suggests that G2 is the acyl O-glucuronide of T-5224.…”

Current applications of high-resolution mass spectrometry in drug metabolism studies

“…An additional benefit of using a harder, nonselective fragmentation followed by a fullscan data acquisition or data-dependent acquisition in LC-HRMS is the fact that the acquired data can be evaluated even retrospectively on unexpected metabolites/analytes. Fragmentrich spectra suitable for data interpretation were also described by Plumb et al [34] using alternating high-low collision energies produced in the collision cell of a Q-TOF instrument.…”