Resolution of indobufen enantiomers by capillary zone electrophoresis. Pharmacokinetic studies of human serum.
A direct and stereospecific method was worked out to quantify indobufen enantiomers in human serum using capillary zone electrophoresis (CZE). The indobufen enantiomers and (+)-S-ketoprofen (internal standard, IS) were separated in a fused silica capillary, filled with heptakis 2,3,6-tri-O-methyl-beta-cyclodextrin as a chiral selector in a buffer of pH 5.0. Indobufen enantiomers and other non-steroidal anti-inflammatory drugs: flurbiprofen, ketoprofen and (+)-S-naproxen were also separated during one analytical run. UV absorbances of indobufen enantiomers were measured at 282 nm. Influence of temperature on resolution of the enantiomers, and the electrophoretic parameters: electrophoretic (muep) and electroosmotic (muEOF) mobilities were also determined. Validation of the method was carried out. Calibration curves of indobufen enantiomers were linear in the range of 0.2-20.0 microg/ml. Percent recovery of both enantiomers from acidified serum was calculated after extraction with methylene chloride. Intra- and inter-day measurement precision and accuracy were below 15.0%. Limits of quantitation and detection were also estimated. The elaborated method was tested in vivo after administration of a single dose of 200 mg rac-indobufen tablets to healthy volunteers. Calculated parameters confirmed usefulness of the method in human pharmacokinetic studies on indobufen enantiomers. The direct CZE method can provide an alternative to HPLC, where enantiomers used to be derivatised before determination.
Główka
Franciszek K
FK
Department of Physical Pharmacy and Pharmacokinetics, University of Medical Sciences, 6 Swiecickiego Street, 60-781 Poznań, Poland. glowka@amp.edu.pl
Karaźniewicz
Marta
M
D016861:Cyclooxygenase Inhibitors / Q000097:blood / Q000302:isolation & purification* / Q000493:pharmacokinetics; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D054833:Isoindoles; D010654:Phenylbutyrates / Q000097:blood / Q000302:isolation & purification* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
D016861:Cyclooxygenase Inhibitors; D054833:Isoindoles; D010654:Phenylbutyrates; C020371:indobufen