Background: Ketorolac, a potent nonsteroidal anti-inflammatory drug used for pain control in children, exists as a racemate of inactive R (+) and active S (-) enantiomers. Aim: To develop a microsampling assay for the enantioselective analysis of ketorolac in children. Methods: Ketorolac enantiomers were extracted from 50 mu l of plasma by liquid-liquid extraction and separated on a ChiralPak AD-RH. Detection was by a TSQ quantum triple quadrupole mass spectrometer with an electrospray ionisation source operating in a positive ion mode. Five children (age 13.8 (1.6) years, weight 52.7 (7.2) kg), were administered intravenous ketorolac 0.5mg/kg (maximum 10mg) and blood samples were taken at 0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12h post administration. CL, V-D and t(1/2) were calculated based on non-compartmental methods. Results: The standard curves for R (+) and S (-) ketorolac were linear in the range 0-2000ng/ml. The LLOQs of the method were 0.15ng on column and 0.31ng on column for R (+) and S (-) ketorolac, respectively. The median (range) V-D and CL of R (+) and S (-) ketorolac were 0.12l/kg (0.07-0.17), 0.017l/h/kg (0.12-0.29) and 0.17 (0.09-0.31) l/kg, 0.049 (0.02-0.1) l/h/kg, p=0.043), respectively. The median (range) elimination half-life (t(1/2)) of the R (+) and S (-) ketorolac was 5.0h (2.5-5.8) and 3.1h (1.8-4.4), p=0.043), respectively. Conclusion: The development of a simple, rapid and reliable ketorolac assay suitable for paediatric PK studies is reported. Copyright (c) 2013 John Wiley & Sons, Ltd.
- volume of distribution
- intravenous ketorolac
- stereoselective pharmacokinetics
- postoperative pain