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

Baba S. Mohammed, Thomas Engelhardt, Gary A. Cameron, Ahmed F. Hawwa, Peter J. Helms, James S. McLay

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)377-386
Number of pages10
JournalBiopharmaceutics & Drug Disposition
Volume34
Issue number7
Early online date14 Aug 2013
DOIs
Publication statusPublished - Oct 2013

Keywords

  • enantioselective
  • ketorolac
  • intravenous
  • pharmacokinetics
  • children
  • volume of distribution
  • clearance
  • half-life
  • intravenous ketorolac
  • stereoselective pharmacokinetics
  • liquid-chromatography
  • postoperative pain
  • tromethamine
  • morphine
  • plasma

Cite this

@article{2e0701853ebb4ff69bddc2903eb8bbce,
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. 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.",
keywords = "enantioselective, ketorolac, intravenous, pharmacokinetics, children, volume of distribution, clearance, half-life, intravenous ketorolac, stereoselective pharmacokinetics, liquid-chromatography, postoperative pain, tromethamine, morphine, plasma",
author = "Mohammed, {Baba S.} and Thomas Engelhardt and Cameron, {Gary A.} and Hawwa, {Ahmed F.} and Helms, {Peter J.} and McLay, {James S.}",
year = "2013",
month = "10",
doi = "10.1002/bdd.1852",
language = "English",
volume = "34",
pages = "377--386",
journal = "Biopharmaceutics & Drug Disposition",
issn = "0142-2782",
publisher = "Wiley",
number = "7",

}

TY - JOUR

T1 - Development of an enantiomer selective microsampling assay for the quantification of ketorolac suitable for paediatric pharmacokinetic studies

AU - Mohammed, Baba S.

AU - Engelhardt, Thomas

AU - Cameron, Gary A.

AU - Hawwa, Ahmed F.

AU - Helms, Peter J.

AU - McLay, James S.

PY - 2013/10

Y1 - 2013/10

N2 - 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.

AB - 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.

KW - enantioselective

KW - ketorolac

KW - intravenous

KW - pharmacokinetics

KW - children

KW - volume of distribution

KW - clearance

KW - half-life

KW - intravenous ketorolac

KW - stereoselective pharmacokinetics

KW - liquid-chromatography

KW - postoperative pain

KW - tromethamine

KW - morphine

KW - plasma

U2 - 10.1002/bdd.1852

DO - 10.1002/bdd.1852

M3 - Article

VL - 34

SP - 377

EP - 386

JO - Biopharmaceutics & Drug Disposition

JF - Biopharmaceutics & Drug Disposition

SN - 0142-2782

IS - 7

ER -