Supercritical fluid chromatography tandem mass spectrometry employed with evaporation-free liquid-liquid extraction for the rapid analysis of cinnarizine in rat plasma

Cinnarizine is a weak base, which can produce supersaturation and precipitation during gastrointestinal transit, affecting its absorption in vivo. Therefore, it is necessary to investigate whether the oral bioavailability of cinnarizine can be improved after co-administration with precipitation inhibitors or not. In order to evaluate the pharmacokinetic behavior of cinnarizine in rats, a simple, rapid, sensitive, and environmentally friendly supercritical fluid chromatography-tandem mass spectrometric method was established and validated. In this method, flunarizine, a structural analogue of cinnarizine, was selected as the internal standard, and cinnarizine was extracted from rat plasma using evaporation-free liquid-liquid extraction method. The analytes were separated on a Torus 1-AA column (3.0 mm x 100 mm, 1.7 mu m) within 2.0 min, using a gradient elution procedure. The transitions of cinnarizine and flunarizine were m/z 369.1 -> 167.1 and m/z 405.1 -> 203.1, respectively. Cinnarizine showed good linear correlation in the range of 1-500 ng/ml with a lower limit of quantification of 1 ng/ml. The intra- and interday precision and accuracy of all quality control samples were within +/- 15%. This high-throughput, accurate, sensitive, and reproducible method has been successfully applied to study the effects of the precipitation inhibitor cinnarizine on the pharmacokinetics in rats.