Simultaneous estimation of E- and Z-isomers of guggulsterone in rabbit plasma using liquid chromatography tandem mass spectrometry and its application to pharmacokinetic study

A sensitive and selective liquid chromatography/tandem mass spectrometric method was developed for simultaneous determination of E‐ and Z‐guggulsterone isomers (antihyperlipidemic drug) in rabbit plasma. Both the isomers were resolved on a Symmetry‐Shield C₁₈ (5 µm, 4.6 × 150 mm) column, using gradient elution comprising a mobile phase of methanol, 0.5% v/v formic acid and acetonitrile. With dexamethasone as internal standard, plasma samples were extracted by an automated solid‐phase extraction method using C₁₈ cartridges. Detection was performed by electrospray ionization in multiple reaction monitoring (MRM) in positive mode. The calibration curve was linear over the concentration range of 1.56–200 ng/mL (r² ≥ 0.998) for both analytes. The intra‐day and inter‐day accuracy and precision were within −0.96 to 4.12 (%bias) and 2.73 to 8.00 (%RSD) respectively. The analytes were stable after three freeze–thaw cycles. The method was successfully applied to study steriospecific pharmacokinetics of E‐ and Z‐guggulsterone in NZ rabbit. Copyright © 2011 John Wiley & Sons, Ltd.