Rapid determination of isocorydine in rat plasma and tissues using liquid chromatography – tandem mass spectrometry and its applications to pharmacokinetics and tissue distribution

Abstract

1. A rapid and sensitive method for the determination of isocorydine in rat plasma and tissues was developed using liquid chromatography–tandem mass spectrometry (LC–MS/MS).

2. The biological samples were processed by extracting with diethyl ether–dichloromethane (3:2, v/v) and tetrahydropulmatine was used as the internal standard (IS). Detection of the analytes was achieved using positive ion mode electrospray ionization in the multiple reaction monitoring mode. The MS/MS ion transitions monitored were m/z 342.0→279.0 and 356.0→191.9 for isocorydine and IS, respectively.

3. The maximum plasma concentration (C_max 2496.8 ± 374.4 µg/L) was achieved at 0.278 ± 0.113 h (T_max) and the half-life (t_1/2) of isocorydine was 0.906 ± 0.222 h after a 20 mg/kg oral administration. As for a 2 mg/kg intravenous (i.v.) administration, the C_max and clearance (CL) were 1843.3 ± 338.3 µg/L and 2.381 ± 0.356 L/h/kg, respectively. Based on the AUC_0–∞ obtained from oral and i.v. administration, the absolute bioavailability (F) was estimated as 33.4%. Tissue distribution results indicated that isocorydine underwent a rapid and wide distribution into tissues and it could effectively cross the blood-brain barrier.

Keywords::

• Isocorydine
• determination
• rat plasma
• pharmacokinetics
• LC–MS
• tissue distribution