Enantioselective analysis of etodolac in human plasma by LC–MS/MS: Application to clinical pharmacokinetics

Publication date: 20 February 2016 Source:Journal of Pharmaceutical and Biomedical Analysis, Volume 120 Author(s): Carolina de Miranda Silva, Adriana Rocha, Eduardo Tozatto, Lucienir Maria da Silva, Eduardo Antônio Donadi, Vera Lucia Lanchote 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: AUC0–∞49.80 versus 4.55ugh/mL;400mg dose: AUC0–∞ 63...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research