DETERMINATION BY HPLC WITH ELECTROCHEMICAL DETECTION OF FORMOTEROL RRAND SS ENANTIOMERS IN URINE

A method is described for the determination of the R,R- and S,S-enanti omer of the long-acting beta 2-adrenoceptor agonist formoterol, which is marketed as a racemate for the treatment of asthma. The methodology is a modification of a previously published assay for formoterol. The sample clean-up from urine takes place by liquid liquid extraction fo llowed by solid phase extraction. An AGP-column combined with electroc hemical detection is used for the separation and detection of the enan tiomers. A diastereomer of formoterol (R,S- or S,R- configuration) is used as internal standard. The lower limits of detection of R,R-formot erol and S,S-formoterol were 60 and 75 pmol/L respectively. The method was validated by a cross-check of spiked urine samples with a GC/MS m ethod for ''racemic'' formoterol (correlation of the sum of the enanti omers measured by HPLC with GC/MS results: r=0.999, n=17). The method appears to be well suited for pharmacokinetic studies of formoterol en antiomers in human subjects after inhalation of therapeutic doses of f ormoterol.