Development and validation of a sensitive LC–MS/MS method for the determination of fenoterol in human plasma and urine samples

Abstract

Due to the lack of sensitivity in current methods for the determination of fenoterol (Fen). A rapid, LC-MS/MS method was developed for the determination of (R,R′)-Fen and (R,R′;S,S′)-Fen in plasma and urine. The method was fully validated and was linear from 50 pg/ml to 2000 pg/ml for plasma and from 2.500 ng/ml to 160 ng/ml for urine with a lower limit of quantitation of 52.8 pg/ml in plasma. The coefficient of variation was <15% for the high QC standards and <10% for the low QC standards in plasma and was <15% for the high and low QC standards in urine. The relative concentrations of (R,R′)-Fen and (S,S′)-Fen were determined using a chirobiotic T chiral stationary phase. The method was used to determine the concentration of (R,R′)-Fen in plasma and urine samples obtained in an oral cross-over study of (R,R′)-Fen and (R,R′;S,S′)-Fen formulations. The results demonstrated a potential pre-systemic enantioselective interaction in which the (S,S′)-Fen reduces the sulfation of the active (R,R′)-Fen. The data suggests that a non-racemic mixture of the Fen enantiomers may provide better bioavailability of the active (R,R′)-Fen for use in the treatment of cardiovascular disease

Chirality of β2-agonists. An overview of pharmacological activity, stereoselective analysis, and synthesis

“…Concerning biodegradation and environmental fate, the recognition of enantioselectivity is essential to provide a more realistic risk assessment of chiral compounds [79]. Several different technologies have been reported for the enantioseparation of β 2 -agonists enantiomers, including predominantly liquid chromatography (LC, HPLC) using chiral stationary phase (CSP) [80] or derivatizing reagents [81] as well as GC, TLC, and capillary electrophoresis (CE) using cyclodextrins or their derivatives as chiral selectors [63,82].…”

“…The fenoterol enantiomers were determined in plasma using a sensitive chiral LC-MS/MS method [80]. Enantiomers of fenoterol were separated (R s = 1.4) on Astec Chirobiotic T analytical column containing teicoplanin as a chiral selector.…”