Development and Validation of a High-performance Liquid Chromatography Coupled with Ultraviolet Detection Method for the Determination of Isocorydine in Rat Plasma and its Application in Pharmacokinetics

Abstract

A new HPLC-UV method has been developed, validated and applied for the determination of isocorydine (CAS 475-67-2) in rat plasma after oral or intravenous (i. v.) administration. Caffeine was used as the internal standard (IS). The analyte and IS were extracted from rat plasma by liquid-liquid extraction (LLE) with methyl tert-butyl ether and they were separated on an XTerra C18 column (250×4.6 mm, 5 µm, pH 1-12) with UV detection at 264 nm. The mobile phase consisted of methanol and 0.02 mol/L potassium dihydrogen phosphate-phosphoric acid buffer solution (pH 3.2) (30:70, v/v) at a flow rate of 1 mL/min for 8.5 min. The retention times of isocorydine and caffeine were approximately 6.5 and 5.1 min, respectively. The good linearity of the calibration curves was observed over the concentration range of 0.05-8 µg/mL (n=8, r 2≥0.9995). The lower limit of quantification (LLOQ) was 0.05 µg/mL [signal to noise ratio (S/N)≥10], and the limit of detection (LOD) was demonstrated as 0.01 µg/mL (S/N≥3). The mean extraction recovery ranged from 83.7% to 89.5% at 3 quality control (QC) concentrations. Intra-day and inter-day precision (relative standard deviation, RSD%) were within 4.7% and accuracy (relative error, RE%) ranged from -1.2% to 4.5%. The developed method was successfully applied to determination of the pharmacokinetic properties of isocorydine in rats after oral administration at a dose of 20 mg/kg and i. v. injection at 5 mg/kg.

An isocorydine derivative (d-ICD) inhibits drug resistance by downregulating IGF2BP3 expression in hepatocellular carcinoma

“…Our previous study showed that isocorydine (ICD) treatment significantly decreased the percentage of CD133 + cells in HCC [ 11 ]. However, the effective concentration of ICD was too high to be tested in a clinical trial [ 12 , 13 ]. To improve the anticancer activity of ICD, ten ICD derivatives were tested.…”

Study on pharmacokinetics and tissue distribution of the isocorydine derivative (AICD) in rats by HPLC-DAD method

“…This implied that AICD could have fast and long-lasting pharmacological effects in vivo , which would be more effective than ICD. According to the tissue distribution data, we found that AICD did not pass through the BBB, unlike its parent compound ICD 15 , mainly because introducing an acetamino in the D-ring C-8 site of ICD enhanced its polarity and hydrophilicity. The tissue distribution results suggested that the adverse reactions in the central nervous system (such as nausea, vomiting, drowsiness and dizziness) might be reduced when using AICD.…”

“…These findings indicate that ICD might be a potential therapeutic drug for the chemotherapeutic treatment of hepatocellular carcinoma 11 , 12 . However, the short half-life, rapid elimination, and low tolerated dose (LD 50 =32.2 mg/kg in mice 13 ) present limitations to its development as a novel chemotherapy 14 , 15 . In order to improve the anti-cancer activity, increase the tolerated dose, and extend half-life of ICD, we modified the structure of ICD to obtain a series of derivatives.…”

Sensitive analysis of trace caffeine in human serum by HPLC using tetraazacalix[2]arene[2]triazine-modified silica as SPE sorbent

“…To extract and enrich trace-level caffeine from complex samples, accelerated solvent extraction (ASE), liquid-liquid extraction (LLE), and solid-phase extraction (SPE), alone or in combination with other purication steps, are conducted by many laboratories. [26][27][28][29][30][31] ASE and LLE with conventional organic solvent are time-consuming and labor-intensive. Furthermore, these methods can easily lead to caffeine loss in the scavenging process and require large amounts of toxic solvents.…”