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

• DOI: 10.1007/s10337-014-2670-4
• Publication Date: 2014-04-30T11:50:52Z
• Authors: Aida Kulo; Nedzad Mulabegovic; Svjetlana Loga-Zec; Karel Allegaert; Jan de Hoon; Rene Verbesselt
• Keywords: 03 medical and health sciences; 0302 clinical medicine; 6. Clean water; 3. Good health

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.