Tags

Type your tag names separated by a space and hit enter

'N-in-one' strategy for metabolite identification using a liquid chromatography/hybrid triple quadrupole linear ion trap instrument using multiple dependent product ion scans triggered with full mass scan.
Rapid Commun Mass Spectrom. 2007; 21(8):1421-30.RC

Abstract

This paper describes a new strategy that utilizes the fast trap mode scan of the hybrid triple quadrupole linear ion trap (QqQ(LIT)) for the identification of drug metabolites. The strategy uses information-dependent acquisition (IDA) where the enhanced mass scan (EMS), the trap mode full scan, was used as the survey scan to trigger multiple dependent enhanced product ion scans (EPI), the trap mode product ion scans. The single data file collected with this approach not only includes full scan data (the survey), but also product ion spectra rich in structural information. By extracting characteristic product ions from the dependent EPI chromatograms, we can provide nearly complete information for in vitro metabolites that otherwise would have to be obtained by multiple precursor ion scan (prec) and constant neutral loss (NL) analysis. This approach effectively overcomes the disadvantages of traditional prec and NL scans, namely the slow quadrupole scan speed, and possible mass shift. Using nefazodone (NEF) as the model compound, we demonstrated the effectiveness of this strategy by identifying 22 phase I metabolites in a single liquid chromatography/tandem mass spectrometry (LC/MS/MS) run. In addition to the metabolites reported previously in the literature, seven new metabolites were identified and their chemical structures are proposed. The oxidative dechlorination biotransformation was also discovered which was not reported in previous literature for NEF. The strategy was further evaluated and worked well for the fast discovery setting when a ballistic gradient elution was used, as well as for a simulated in vivo setting when the incubated sample (phase I metabolites) was spiked to control human plasma extract and control human urine.

Authors+Show Affiliations

Covance Laboratories Inc., 3301 Kinsman Boulevard, Madison, Wisconsin, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17377936

Citation

Li, Austin C., et al. "'N-in-one' Strategy for Metabolite Identification Using a Liquid Chromatography/hybrid Triple Quadrupole Linear Ion Trap Instrument Using Multiple Dependent Product Ion Scans Triggered With Full Mass Scan." Rapid Communications in Mass Spectrometry : RCM, vol. 21, no. 8, 2007, pp. 1421-30.
Li AC, Gohdes MA, Shou WZ. 'N-in-one' strategy for metabolite identification using a liquid chromatography/hybrid triple quadrupole linear ion trap instrument using multiple dependent product ion scans triggered with full mass scan. Rapid Commun Mass Spectrom. 2007;21(8):1421-30.
Li, A. C., Gohdes, M. A., & Shou, W. Z. (2007). 'N-in-one' strategy for metabolite identification using a liquid chromatography/hybrid triple quadrupole linear ion trap instrument using multiple dependent product ion scans triggered with full mass scan. Rapid Communications in Mass Spectrometry : RCM, 21(8), 1421-30.
Li AC, Gohdes MA, Shou WZ. 'N-in-one' Strategy for Metabolite Identification Using a Liquid Chromatography/hybrid Triple Quadrupole Linear Ion Trap Instrument Using Multiple Dependent Product Ion Scans Triggered With Full Mass Scan. Rapid Commun Mass Spectrom. 2007;21(8):1421-30. PubMed PMID: 17377936.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 'N-in-one' strategy for metabolite identification using a liquid chromatography/hybrid triple quadrupole linear ion trap instrument using multiple dependent product ion scans triggered with full mass scan. AU - Li,Austin C, AU - Gohdes,Mark A, AU - Shou,Wilson Z, PY - 2007/3/23/pubmed PY - 2007/5/30/medline PY - 2007/3/23/entrez SP - 1421 EP - 30 JF - Rapid communications in mass spectrometry : RCM JO - Rapid Commun. Mass Spectrom. VL - 21 IS - 8 N2 - This paper describes a new strategy that utilizes the fast trap mode scan of the hybrid triple quadrupole linear ion trap (QqQ(LIT)) for the identification of drug metabolites. The strategy uses information-dependent acquisition (IDA) where the enhanced mass scan (EMS), the trap mode full scan, was used as the survey scan to trigger multiple dependent enhanced product ion scans (EPI), the trap mode product ion scans. The single data file collected with this approach not only includes full scan data (the survey), but also product ion spectra rich in structural information. By extracting characteristic product ions from the dependent EPI chromatograms, we can provide nearly complete information for in vitro metabolites that otherwise would have to be obtained by multiple precursor ion scan (prec) and constant neutral loss (NL) analysis. This approach effectively overcomes the disadvantages of traditional prec and NL scans, namely the slow quadrupole scan speed, and possible mass shift. Using nefazodone (NEF) as the model compound, we demonstrated the effectiveness of this strategy by identifying 22 phase I metabolites in a single liquid chromatography/tandem mass spectrometry (LC/MS/MS) run. In addition to the metabolites reported previously in the literature, seven new metabolites were identified and their chemical structures are proposed. The oxidative dechlorination biotransformation was also discovered which was not reported in previous literature for NEF. The strategy was further evaluated and worked well for the fast discovery setting when a ballistic gradient elution was used, as well as for a simulated in vivo setting when the incubated sample (phase I metabolites) was spiked to control human plasma extract and control human urine. SN - 0951-4198 UR - https://www.unboundmedicine.com/medline/citation/17377936/'N_in_one'_strategy_for_metabolite_identification_using_a_liquid_chromatography/hybrid_triple_quadrupole_linear_ion_trap_instrument_using_multiple_dependent_product_ion_scans_triggered_with_full_mass_scan_ L2 - https://doi.org/10.1002/rcm.2976 DB - PRIME DP - Unbound Medicine ER -