Drug Metabolite detection
Enhance LC-MS determination of drug metabolites in urine using ultraFAIMS
Enhanced performance in the determination of ibuprofen 1-β-O-acyl glucuronide in urine by combining high field asymmetric waveform ion mobility spectrometry with liquid chromatography-time-of-flight mass spectrometry
Robert W. Smith, Danielle E. Toutoungi, James C. Reynolds, Anthony W.T. Bristow, Andrew Ray, Ashley Sage, Ian D. Wilson, Daniel J. Weston, Billy Boyle, Colin S. Creaser,
The addition of an ultraFAIMS pre-separation stage into the electrospray ionisation (ESI) source of an LC-ESI-MS improves the qualitative and quantitative of analysis of drug metabolites such as (R/S) ibuprofen 1-beta-O-acyl glucuronide (IAG) in urine, giving lower LOQ, increased LDR, better reproducibility, reduced matrix chemical noise.
UltraFAIMS allows analytes of interest to be separated from co-eluting species based on the differing mobilities of analyte ions subjected to a powerful oscillating electric field whilst in a flow of carrier gas. UltraFAIMS technology uses chips with multiple narrow separation channels, rather than a single wider gap. This avoids ion current limitations that are seen in single channel FAIMS instruments. Higher electric fields allow extremely fast quantitative measurements, as well as the potential for separation of a wider range of analytes.
UltraFAIMS can be used to reduce background ‘chemical noise’ and separate isobaric analytes. This makes it ideal for separating drug metabolites from complex biological samples such as urine, blood, breath condensate etc. Results of a study published in the Journal of Chromatography A show that the addition of an ultraFAIMS unit between an Agilent 1200 series HPLC and an Agilent 6230 time-of-flight mass spectrometer fitted with a JetStream ESI source resulted in a lower LOQ (limit of quantitation), increased LDR (linear dynamic range), better reproducibility, reduced matrix chemical noise when quantifying drug metabolite (R/S) ibuprofen 1-beta-O-acyl glucuronide (IAG) in urine. In-source collision induced dissociation of the FAIMS-selected deprotonated metabolite was used to fragment the ion prior to mass analysis, enhancing selectivity by removing co-eluting species and aiding the qualitative identification of the metabolite by increasing the signal-to-noise ratio of the fragment ions. (Figure 1).