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

Aida Kulo*, Nedzad Mulabegovic, Svjetlana Loga-Zec, Karel Allegaert, Jan De Hoon, Rene Verbesselt

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)803-812
Number of pages10
JournalChromatographia
Volume77
Issue number11-12
DOIs
Publication statusPublished - Jun 2014
Externally publishedYes

Bibliographical note

Funding Information:
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 Investigator-ship (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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