A fast and simple liquid chromatography–mass spectrometry method for the determination of lycorine in mice plasma and tissues was developed and well used in the pharmacokinetic and tissue distribution study of lycorine after tail vein injection and intraperitoneal administration. Biological samples were processed with ethyl acetate by liquid–liquid extraction, and evodiamine was used as the internal standard. Chromatographic separation was performed on an Amethyst C18 column (4.6×150 mm) with a mobile phase consisting of methanol and water. Quantification was performed by selected ion monitoring with m / z 288 [M+H] + for lycorine and m / z 304 [M+H] + for the internal standard. Good linearity was observed over the concentration ranges. Limits of quantification were low up to 10.0 ng/mL in plasma samples, 9.0 ng/g for lung, 12.0 ng/g for heart, 18.0 ng/g for spleen and 6.5 ng/g for other tested tissues. The intraday accuracy and precision in plasma and tissues ranged from −7.4% to 9.1%. Recoveries in plasma and tissue were more than 80%. The method was rapid, accurate and fully validated. It was successfully applied to the investigation of the pharmacokinetics and tissue distribution of lycorine in mice.
A simple, rapid and sensitive high-performance liquid chromatography–tandem mass spectrometric (HPLC–MS/MS) method was developed and validated for determining lycorine in rat plasma. Plasma samples were prepared by a simple protein precipitation with methanol containing dextrorphan as internal standard. The chromatographic separation was performed on a Kromasil 60-5CN column (3 μm, 2.1 mm × 150 mm) with the mobile phase of methanol/water (containing 0.1% formic acid) (40:60, v/v) at a flow rate of 0.2 mL/min, the total analytical runtime was 5 min. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with Electronic Spray Ion by selected reaction monitoring (SRM) of the transitions at m / z 288.1 → 147.1 for lycorine and m / z 258.1 → 157.2 for dextrorphan, respectively. The calibration curve was linear over the range of 1–1000 ng/mL with the lower limit of quantification of 1 ng/mL for lycorine. The intra- and inter-day precision (R.S.D.%) were less than 8.5% and accuracy (R.E.%) was within ±7.0%. Lycorine was sufficiently stable under all relevant analytical conditions. This method was successfully applied to the pharmacokinetic study of lycorine in rats after intraperitoneal administration with different doses of 5, 10 and 20 mg/kg.
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