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J Pharm Biomed Anal. 2014 Sep;98:387-92. doi: 10.1016/j.jpba.2014.06.024. Epub 2014 Jun 21.

Enantioselective determination of ibuprofen in saliva by liquid chromatography/tandem mass spectrometry with chiral electrospray ionization-enhancing and stable isotope-coded derivatization.

Author information

1
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
2
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. Electronic address: higashi@rs.tus.ac.jp.

Abstract

A method was developed and validated for the enantioselective determination of trace ibuprofen (IBU) in saliva using liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) combined with the derivatization using a chiral ESI-enhancing reagent, (S)-1-(4-dimethylaminophenylcarbonyl)-3-aminopyrrolidine (DAPAP), and its isotope-coded analog, (2)H4-DAPAP (d-DAPAP). The DAPAP-derivatization enabled the highly sensitive detection [detection limit, 0.15fmol (equivalent to 30fg of intact IBU) on the column] and complete separation (resolution 3.1) of the IBU enantiomers. The use of d-DAPAP significantly improved the assay precision and accuracy; the intra- (n=5) and inter-assay (n=5) relative standard deviations did not exceed 6.2%, and good accuracy (101.3-106.1%) was obtained. The developed method was successfully applied to the quantitative analysis of IBU in saliva. Using this method, salivary concentration-time profiles of each enantiomer after a single oral administration of the racemic IBU to healthy subjects were obtained. The area under the salivary concentration-time curve of the (S)-enantiomer was ca. twice that of the (R)-enantiomer due to the unidirectional chiral inversion of the (R)- to (S)-enantiomer in vivo. Thus, saliva-based noninvasive pharmacokinetic analyses of IBU enantiomers were achieved by this method.

KEYWORDS:

Enantiomeric separation; Ibuprofen; LC/ESI-MS/MS; Saliva; Stable isotope-coded derivatization

PMID:
24999866
DOI:
10.1016/j.jpba.2014.06.024
[Indexed for MEDLINE]

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