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A Validated Enantioselective Assay for the Determination of Ibuprofen in Human Plasma Using Ultra Performance Liquid Chromatography with Tandem Mass Spectrometry (UPLC-MS/MS)

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DOI: 10.4236/ajac.2010.12007    5,892 Downloads   12,364 Views   Citations

ABSTRACT

A modified ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitation of ibuprofen enantiomers in human plasma. Ibuprofen and flurbiprofen (internal standard) were extracted from human plasma at acidic pH, using a single-step liquid-liquid extraction with methyl-tert-butyl ether. The enantiomers of ibuprofen and flurbiprofen were derivatized to yield the corresponding diastereomers. Chromatographic separation was achieved using a phenyl column with a run time of 20 min. (R)- and (S)-ibuprofen were quantitated at the multiple reaction monitoring (MRM) transition of m/z 360.2 ? 232.1, and (R)- and (S)-flurbiprofen were monitored at the MRM transition of m/z 398.3 ? 270.1. The method was validated for accuracy, precision, linearity, range, limit of quantitation (LOQ), limit of detection (LOD), selectivity, absolute recovery, matrix effect, dilution integrity, and evaluation of carry-over. Accuracy for (R)-ibuprofen ranged between –11.8% and 11.2%, and for (S)-ibuprofen between –8.6% and –0.3%. Precision for (R)-ibuprofen was ≤ 11.2%, and for (S)-ibuprofen ≤ 7.0%. The calibration curves were weighted (1/X2, n = 7) and were linear with r2 for (R)-ibuprofen ≥ 0.988 and for (S)-ibuprofen ≥ 0.990. The range of the method was 50 to 5000 ng/mL with the LOQ of 50 ng/mL, and LOD of 1 ng/mL, for (R)- and (S)-ibuprofen requiring 100 µL of sample. The method was applied successfully to a pharmacokinetic study with the administration of a single oral dose of ibuprofen capsules to human subjects.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

A. Szeitz, A. Edginton, H. Peng, B. Cheung and K. Riggs, "A Validated Enantioselective Assay for the Determination of Ibuprofen in Human Plasma Using Ultra Performance Liquid Chromatography with Tandem Mass Spectrometry (UPLC-MS/MS)," American Journal of Analytical Chemistry, Vol. 1 No. 2, 2010, pp. 47-58. doi: 10.4236/ajac.2010.12007.

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