In:
Journal of Separation Science, Wiley, Vol. 32, No. 13 ( 2009-07), p. 2209-2217
Abstract:
This article describes the application of a recently developed general unknown screening (GUS) strategy based on LC coupled to a hybrid linear IT‐triple quadrupole mass spectrometer (LC‐MS/MS‐LIT) for the simultaneous detection and identification of drug metabolites following in vitro incubation with human liver microsomes. The histamine H1 receptor antagonist loratadine was chosen as a model compound to demonstrate the interest of such approach, because of its previously described complex and extensive metabolism. Detection and mass spectral characterization were based on data‐dependent acquisition, switching between a survey scan acquired in the ion‐trapping Q3 scan mode with dynamic subtraction of background noise, and a dependent scan in the ion‐trapping product ion scan mode of automatically selected parent ions. In addition, the MS 3 mode was used in a second step to confirm the structure of a few fragment ions. The sensitivity of the ion‐trapping modes combined with the selectivity of the triple quadrupole modes allowed, with only one injection, the detection and identification of 17 phase I metabolites of loratadine. The GUS procedure used in this study may be applicable as a generic technique for the characterization of drug metabolites after in vitro incubation, as well as probably in vivo experiments.
Type of Medium:
Online Resource
ISSN:
1615-9306
,
1615-9314
DOI:
10.1002/jssc.200900099
Language:
English
Publisher:
Wiley
Publication Date:
2009
detail.hit.zdb_id:
2047990-6
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