Development of an enantiomer selective microsampling assay for the quantification of ketorolac suitable for paediatric pharmacokinetic studies

• Published in: Biopharmaceutics & drug disposition Vol. 34; no. 7; pp. 377 - 386
• Main Authors: Mohammed, Baba S., Engelhardt, Thomas, Cameron, Gary A., Hawwa, Ahmed F., Helms, Peter J., McLay, James S.
• Format: Journal Article
• Language: English
• Published: Chichester Blackwell Publishing Ltd 01.10.2013; Wiley; Wiley Subscription Services, Inc
• Subjects: Adolescent; Anti-Inflammatory Agents, Non-Steroidal - blood; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Biological and medical sciences; Biological Assay; Child; children; clearance; enantioselective; Half-Life; Humans; intravenous; ketorolac; Ketorolac - blood; Ketorolac - chemistry; Ketorolac - pharmacokinetics; Medical sciences; pharmacokinetics; Pharmacology. Drug treatments; Stereoisomerism; volume of distribution; Human; Prostaglandin-endoperoxide synthase; Intravenous administration; Enantioselectivity; volume of distribution; Enzyme; Ketorolac; Enzyme inhibitor; Clearance; half-life; Non steroidal antiinflammatory agent; Analgesic; Distribution volume; intravenous; children; Enantiomer; Antipyretic; Oxidoreductases; Pharmacokinetics; Child; Half life; enantioselective
• ISSN: 0142-2782; 1099-081X
• DOI: 10.1002/bdd.1852

ABSTRACT 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 µl 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 0.5 mg/kg (maximum 10 mg) and blood samples were taken at 0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 h post administration. CL, VD and t1/2 were calculated based on non‐compartmental methods. Results: The standard curves for R (+) and S (‐) ketorolac were linear in the range 0–2000 ng/ml. The LLOQs of the method were 0.15 ng on column and 0.31 ng on column for R (+) and S (‐) ketorolac, respectively. The median (range) VD and CL of R (+) and S (‐) ketorolac were 0.12 l/kg (0.07–0.17), 0.017 l/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 (t1/2) of the R (+) and S (‐) ketorolac was 5.0 h (2.5–5.8) and 3.1 h (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 © 2013 John Wiley & Sons, Ltd.