Determination of rat plasma levels of sertraline enantiomers using direct injection with achiral-chiral column switching by LC-ESI/MS/MS.

A highly sensitive and selective on-line two-dimensional reversed-phase liquid chromatography/electrospray ionization-tandem mass spectrometric (2D-LC-ESI/MS/MS) method to determine sertraline (SRT) enantiomers in rat plasma was developed and validated. The method was applied to separate and determine the diastereomers and enantiomers of SRT simultaneously. The 2D-LC-ESI/MS/MS system consisted of RAM column in first dimension for trapping proteineous part of plasma and a chiral Cyclobond column as second dimension for separation of enantiomers and diastereomers of SRT using 0.1% aqueous trifluoroacetic acid:acetonitrile (86:14, v/v) as mobile phase in an isocratic elution mode. The linear dynamic range was 0.5-200ng/mL (r(2)>0.999). Acceptable precision and accuracy were obtained over the calibration range. The assay was successfully used in the analysis of SRT enantiomers in rat plasma to support pharmacokinetic studies.