Enantioselective analysis of etodolac in human plasma by LC-MS/MS : Application to clinical pharmacokinetics
Copyright © 2015 Elsevier B.V. All rights reserved..
Etodolac is a non-steroidal anti-inflammatory drug with preferential inhibition of cyclooxigenase-2 and is widely used in the management of pain in patients with inflammatory arthritis. Etodolac is available as a racemic mixture of (-)-(R)-Etodolac and (+)-(S)-Etodolac; cyclooxigenases inhibition is attributed to (+)-(S)-Etodolac. According to our knowledge, this is the first method for determination of etodolac enantiomers in plasma using LC-MS/MS. Plasma extraction were performed with 25μL of plasma and 1mL of n-hexane:ethyl acetate (95:5); racemic ibuprofen was used as internal standard. Resolution of enantiomers were performed in a Chiralcel(®)OD-H column; deprotonated [M-H](-) and their respective ion products were monitored at transitions of 286>242 for etodolac enantiomers and 205>161 for ibuprofen. The quantitation limit was 3.2ng/mL for both enantiomers in plasma. The method was applied to study the pharmacokinetics of etodolac enantiomers after the administration of a 300 and 400mg dose of racemic drug to a healthy volunteer. Analysis of plasma samples showed higher plasma concentration of (-)-(R)-Etodolacfor both doses (300mg dose: AUC(0-∞)49.80 versus 4.55ugh/mL;400mg dose: AUC(0-∞) 63.90 versus 6.00ugh/mL) with an (R)-(+)/(S)-(-) ratio of approximately 11.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:120 |
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| Enthalten in: |
Journal of pharmaceutical and biomedical analysis - 120(2016) vom: 20. Feb., Seite 120-6 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
de Miranda Silva, Carolina [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.10.2016 Date Revised 30.12.2016 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jpba.2015.12.009 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM256071659 |
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| 245 | 1 | 0 | |a Enantioselective analysis of etodolac in human plasma by LC-MS/MS |b Application to clinical pharmacokinetics |
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| 520 | |a Copyright © 2015 Elsevier B.V. All rights reserved. | ||
| 520 | |a Etodolac is a non-steroidal anti-inflammatory drug with preferential inhibition of cyclooxigenase-2 and is widely used in the management of pain in patients with inflammatory arthritis. Etodolac is available as a racemic mixture of (-)-(R)-Etodolac and (+)-(S)-Etodolac; cyclooxigenases inhibition is attributed to (+)-(S)-Etodolac. According to our knowledge, this is the first method for determination of etodolac enantiomers in plasma using LC-MS/MS. Plasma extraction were performed with 25μL of plasma and 1mL of n-hexane:ethyl acetate (95:5); racemic ibuprofen was used as internal standard. Resolution of enantiomers were performed in a Chiralcel(®)OD-H column; deprotonated [M-H](-) and their respective ion products were monitored at transitions of 286>242 for etodolac enantiomers and 205>161 for ibuprofen. The quantitation limit was 3.2ng/mL for both enantiomers in plasma. The method was applied to study the pharmacokinetics of etodolac enantiomers after the administration of a 300 and 400mg dose of racemic drug to a healthy volunteer. Analysis of plasma samples showed higher plasma concentration of (-)-(R)-Etodolacfor both doses (300mg dose: AUC(0-∞)49.80 versus 4.55ugh/mL;400mg dose: AUC(0-∞) 63.90 versus 6.00ugh/mL) with an (R)-(+)/(S)-(-) ratio of approximately 11 | ||
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| 650 | 4 | |a LC–MS/MS | |
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| 700 | 1 | |a Rocha, Adriana |e verfasserin |4 aut | |
| 700 | 1 | |a Tozatto, Eduardo |e verfasserin |4 aut | |
| 700 | 1 | |a da Silva, Lucienir Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Donadi, Eduardo Antônio |e verfasserin |4 aut | |
| 700 | 1 | |a Lanchote, Vera Lucia |e verfasserin |4 aut | |
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