title: Development of an enantiomer selective microsampling assay for the quantification of ketorolac suitable for paediatric pharmacokinetic studies.
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.
  
  
  OBJECTIVE
  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 0.5mg/kg (maximum 10mg) 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.
  
  
  CONCLUSIONS
  The development of a simple, rapid and reliable ketorolac assay suitable for paediatric PK studies is reported.
authors.forename: Baba S
authors.initials: BS
authors.lastname: Mohammed
authors.forename: Thomas
authors.initials: T
authors.lastname: Engelhardt
authors.forename: Gary A
authors.initials: GA
authors.lastname: Cameron
authors.forename: Ahmed F
authors.initials: AF
authors.lastname: Hawwa
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Helms
authors.forename: James S
authors.initials: JS
authors.lastname: McLay
mesh_terms: D000293:Adolescent; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D001681:Biological Assay; D002648:Child; D006207:Half-Life; D006801:Humans; D020910:Ketorolac / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D013237:Stereoisomerism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D020910:Ketorolac