Analytical studies on beta-lactam antibiotics. III. Automated high-performance liquid chromatographic method for the determination of the orally active antibiotic ceftibuten in human plasma and urine.
A fully automated high-performance liquid chromatographic method was established for the determination of the oral cephalosporin antibiotic ceftibuten. The procedure for plasma assay involves on-line sample clean-up with a precolumn of BSA-ODS (ODS coated with bovine serum albumin) and subsequent determination of the drug with a reversed-phase C18 column using a column-switching technique. The precolumn effectively removed protein components and hydrophilic substances from plasma, with ceftibuten and its metabolite, the trans-isomer of ceftibuten, being retained using an ion-pairing reagent, tetra-n-butylammonium bromide, in the mobile phase. In urine assay, an ODS precolumn was used in place of the BSA-ODS column. The urine sample, after 10-fold dilution, was analysed in a similar manner to that used in the plasma assay. A large proportion of hydrophilic substances was eliminated by the on-line clean-up and the residual interfering substances introduced into the analytical column were separated from ceftibuten and its metabolite using the ion-pairing reagent. This method permits the determination of 0.1-20 micrograms/ml of ceftibuten and its metabolite in human plasma and 1-200 micrograms/ml of both compounds in urine. The advantages of the method are easy performance without manual sample preparation, saving of plasma (50 microliters) and high sensitivity. The method was applied to pharmacokinetic studies of ceftibuten after oral administration to healthy subjects.
Matsuura
A
A
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Nagayama
T
T
Kitagawa
T
T
D000284:Administration, Oral; D001331:Automation; D000077722:Ceftibuten; D002511:Cephalosporins / Q000032:analysis* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D006801:Humans
D002511:Cephalosporins; D000077722:Ceftibuten