Enantioselective pharmacokinetics of mabuterol in rats studied using sequential achiral and chiral HPLC

Abstract

The enantioselective pharmacokinetics of mabuterol was studied in six rats after single oral dose administration of mabuterol racemate. Serial plasma samples were collected and the pharmacokinetic behavior of each enantiomer in rats was characterized using a sequential achiral and chiral liquid chromatographic method. This method involved the separation of mabuterol racemate from endogenous substances on an achiral ODS column and enantiomeric separation on a Chirobiotic V column. The plasma-concentration data were analyzed for individual mabuterol enantiomer using 3P97 software. After i.g. administration of mabuterol racemate at a dose of 10 mg/kg, both enantiomers were slowly absorbed, reaching mean C(max) of 266.8 and 277.9 ng/mL at t(max) of 5.3 and 5.7 h for R- and S-mabuterol, respectively. The AUC(0-infinity) (5,938.9 ng h/mL) of R-mabuterol was significantly higher than that (4,446.1 ng h/mL) of S-mabuterol, and the half-life (14.5 h) was longer than that (9.6 h) of S-mabuterol (p < 0.001 and p < 0.01, respectively), showing that enantioselective pharmacokinetics between mabuterol enantiomers occur during the metabolism phase.

Development and validation of enantioselective high performance liquid chromatographic method for Valacyclovir, an antiviral drug in drug substance

“…The development of analytical methods for the quantitative analysis of chiral materials and for the assessment of enantiomeric purity is extremely challenging due to the fact that enantiomers possess virtually identical properties [8]. Recently, much work has been reported describing the use of chiral stationary phases, in conjunction with HPLC, as a way to separate and thereby individually quantitate the enantiomers of an enantiomeric pair [9][10][11].…”

Determination of tenatoprazole enantiomers and their enantioselective pharmacokinetics in rats

“…11,12 In this study, the tenatoprazole mixture was rapidly resolved from the endogenous matrix and quantified on an achiral system. The eluted fractions containing the tenatoprazole mixture were collected, evaporated, reconstituted with the chiral mobile phase and injected into a chiral system where the enantiomeric ratio was determined.…”

Supramolecular Systems-Based HPLC for Chiral Separation of Beta-Adrenergics and Beta-Adrenolytics in Drug Discovery Schemes

“…The detection was achieved by fluorescence at excitation/emission wavelength 275/305 nm. Lu et al [63] studied enantioseparation of beta-adrenergic mabuterol by using a sequential achiral and chiral liquid chromatographic methods (ODS and Chirobiotic-V columns). Bartolincic et al [64] resolved beta-adrenergic albuterol on Chirobiotic-V column.…”