Quantitative determination of oseltamivir and oseltamivir carboxylate in human fluoride EDTA plasma including the ex vivo stability using high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry

W. Kromdijk, H. Rosing, M. P.H. van den Broek, J. H. Beijnen, A. D.R. Huitema

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

19 Citaten (Scopus)

Samenvatting

Oseltamivir, the ethyl ester prodrug of the neuramidase inhibitor oseltamivir carboxylate, is licensed for the treatment of patients with influenza virus infection. Here we describe the development and validation of an assay for the simultaneous quantification of oseltamivir and oseltamivir carboxylate in human fluoride EDTA plasma including the ex vivo stability using liquid chromatography coupled to tandem mass spectrometry. Sample pretreatment consisted of protein precipitation with 8% (v/v) trichloroacetic acid in water using only 50 μL plasma. Chromatographic separation was performed on a reversed phase C18 column (150 mm × 2.0. mm ID, particle size 4 μm) with a stepwise gradient using 0.1% formic acid and methanol at a flow rate of 250 μL/min. A triple quadrupole mass spectrometer operating in the positive ionization mode was used for detection and drug quantification. The method was validated over a range of 3-300. ng/mL for oseltamivir and 10-10,000. ng/mL for oseltamivir carboxylate. Deuterated oseltamivir and oseltamivir carboxylate were used as internal standards. The intra-assay accuracies and precisions for oseltamivir were between -8.8 and 16.3% at the LLOQ level, whereas for all other concentration levels this was -8.6 and 14.5%. For oseltamivir carboxylate the intra-assay accuracies and precisions were between -10.9 and 10.7% at all levels. Furthermore, oseltamivir was stable in plasma and whole blood ex vivo in commercially available fluoride EDTA tubes for at least 24. h at 2-8 °C. This method is now applied for the determination of both compounds in specific patient populations to evaluate current dosing guidelines.

Originele taal-2Engels
Pagina's (van-tot)57-63
Aantal pagina's7
TijdschriftJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume891-892
DOI's
StatusGepubliceerd - 1 apr. 2012
Extern gepubliceerdJa

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