title: Enantioselective analysis of etodolac in human plasma by LC-MS/MS: Application to clinical pharmacokinetics.
abstract: 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.
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: de Miranda Silva
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Rocha
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tozatto
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Lucienir Maria
authors.initials: LM
authors.lastname: da Silva
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Eduardo Antônio
authors.initials: EA
authors.lastname: Donadi
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: lanchote@fcfrp.usp.br.
authors.forename: Vera Lucia
authors.initials: VL
authors.lastname: Lanchote
mesh_terms: D000085:Acetates / Q000737:chemistry; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods; D017308:Etodolac / Q000097:blood* / Q000737:chemistry*; D006586:Hexanes / Q000737:chemistry; D006801:Humans; D007052:Ibuprofen / Q000097:blood / Q000737:chemistry; D008297:Male; D010949:Plasma / Q000737:chemistry*; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006586:Hexanes; C026385:n-hexane; D017308:Etodolac; C007650:ethyl acetate; D007052:Ibuprofen
keywords: Enantiomers; Etodolac; Healthy volunteer; LC–MS/MS; Pharmacokinetics; Plasma