A highly sensitive LC-MS/MS method for the determination of S-citalopram in rat plasma: application to a pharmacokinetic study in rats.

ABSTRACT

A highly sensitive, rapid assay method has been developed and validated for the estimation of S-citalopram (S-CPM) in rat plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive-ion mode. The assay procedure involves a simple liquid-liquid extraction of S-CPM and phenacetin (internal standard, IS) from rat plasma with t-butyl methyl ether. Chromatographic separation was operated with 0.2% formic acidacetonitrile (2080, v/v) at a flow rate of 0.50 mL/min on a Symmetry Shield RP(18) column with a total run time of 3.0 min. The MS/MS ion transitions monitored were 325.26 → 109.10 for S-CPM and 180.10 → 110.10 for IS. Method validation and pre-clinical sample analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.5 ng/mL and the linearity was observed from 0.5 to 5000 ng/mL. The intra- and inter-day precisions were in the range of 1.14-5.56 and 0.25-12.3%, respectively. This novel method has been applied to a pharmacokinetic study and to estimate brain-to-plasma ratio of S-CPM in rats.