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Determination of Racemic Ketorolac, Ketorolac Enantiomers and Their Metabolites in Human Plasma and Urine by LC–UV, Applied in Clinical Study During and After Pregnancy

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Abstract

In order to enhance the sensitivity and to develop a faster direct method for plasma and urine quantification of racemic ketorolac, its metabolites (p-hydroxy-ketorolac and ketorolac glucuronides) and ketorolac enantiomers, we developed an extraction procedure based on solid-phase extraction combined with specific and fast chromatographic separation. Extraction and chromatography resulted in cleaner chromatograms without interfering compounds. In both plasma and urine, linearity of the standard curves for racemic ketorolac and p-hydroxy-ketorolac was validated in the concentration range 0.025–10 mg L−1, while for ketorolac enantiomers in the concentration range 0.025–5 mg L−1. The lower limit of quantification was two times lower than in earlier described methods. The developed method was suitable for direct quantification of racemic ketorolac, p-hydroxy-ketorolac and ketorolac enantiomers in plasma and urine samples in women at delivery and in postpartum, enabling us to document significant intra-individual differences in pharmacokinetics between these physiological states.

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Acknowledgments

The clinical research of Karel Allegaert is supported by the Fund for Scientific Research, Flanders (Belgium) (F.W.O. Vlaanderen) by a Fundamental Clinical Investigatorship (1800214 N), and of Aida Kulo by a JoinEU-SEE scholarship (2009–2010). We would like to thank Sonia Demarsin for her technical assistance. The clinical research was in part supported by an unrestricted grant provided by the Belgian Society for Anesthesia and Resuscitation.

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Authors and Affiliations

  1. Center for Clinical Pharmacology, KU Leuven and University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium

    Aida Kulo, Jan de Hoon & Rene Verbesselt

  2. Faculty of Medicine, Institute of Pharmacology, Clinical Pharmacology and Toxicology, University of Sarajevo, Čekaluša 90, 71000, Sarajevo, Bosnia and Herzegovina

    Aida Kulo, Nedzad Mulabegovic & Svjetlana Loga-Zec

  3. Department of Development and Regeneration, KU Leuven and Neonatology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium

    Karel Allegaert

Authors
  1. Aida Kulo
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  2. Nedzad Mulabegovic
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  3. Svjetlana Loga-Zec
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  4. Karel Allegaert
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  5. Jan de Hoon
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  6. Rene Verbesselt
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Correspondence to Aida Kulo.

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Kulo, A., Mulabegovic, N., Loga-Zec, S. et al. Determination of Racemic Ketorolac, Ketorolac Enantiomers and Their Metabolites in Human Plasma and Urine by LC–UV, Applied in Clinical Study During and After Pregnancy. Chromatographia 77, 803–812 (2014). https://doi.org/10.1007/s10337-014-2670-4

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  • DOI: https://doi.org/10.1007/s10337-014-2670-4

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