Analysis of ibuprofen enantiomers in rat plasma by liquid chromatography with tandem mass spectrometry.
A sensitive and selective method for the analysis of ibuprofen enantiomers by LC-MS/MS was developed and validated for the purpose of application in pharmacokinetic studies in small experimental animals. Aliquots of 200 μL plasma were submitted to liquid-liquid extraction with hexane/diisopropylether (50:50 v/v) in acid pH. Separation was accomplished in a Chirex® 3005 (250 × 4.6 mm, 5 μm) column at 25°C with a mobile phase that consisted of 0.01 M ammonium acetate in methanol at a flow rate of 1.1 mL/min. The mass spectrometer consisted of an ESI interface operating at negative ionization mode and multiple reaction monitoring. The transitions 205 > 161 and 240 > 197 were monitored for ibuprofen enantiomers and fenoprofen (internal standard), respectively. Method validation included the evaluation of the matrix effect, stability, linearity, lower LOQ, within-run and between-run precision, and accuracy. The lower LOQ was 25 ng/mL for each ibuprofen enantiomer, and the calibration curves showed good linearity in the range 0.025-50 μg/mL. The method was successfully applied in the investigation of pharmacokinetic disposition of ibuprofen enantiomers in rats treated orally with 25 mg/kg of the racemate. Enantioselective kinetic disposition was observed with accumulation of (+)-(S)-ibuprofen in rats following single oral administration.
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Brazil.
Juciane Lauren Cavalcanti
JL
Cardoso
Vera Lucia
VL
Lanchote
Maria Paula Marques
MP
Pereira
Natália Valadares
NV
de Moraes
José Salvador
JS
Lepera
D000818:Animals; D002853:Chromatography, Liquid; D007052:Ibuprofen / Q000097:blood* / Q000737:chemistry*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry
D007052:Ibuprofen
Enantiomers; Ibuprofen; Pharmacokinetics; Plasma