Development and application of a liquid chromatography–tandem mass spectrometry method for the analysis of Areca nut alkaloids in rat plasma for a toxicokinetic study

Le résumé fourni par la source

Areca nut (Areca catechu L., Arecaceae) contains bioactive alkaloids, including arecoline, arecaidine, and guvacoline, which are associated with pharmacological and toxicological effects. A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for simultaneous quantification of these alkaloids in rat plasma and was applied to a toxicokinetic study. Chromatographic separation was achieved on a reversed-phase C18 column using gradient elution with aqueous and organic mobile phases containing a volatile acid modifier. Detection was performed by electrospray ionization in the positive ion mode with multiple reaction monitoring, and plasma samples were prepared by protein precipitation. The method was validated according to the current bioanalytical guidelines. The calibration curves showed good linearity (r > 0.99) over the tested ranges, the within- and between-run accuracy and precision were within ±15% (±20% at lower limit of quantification (LLOQ)), and the selectivity, carry-over, recovery, matrix effect, dilution integrity, and stability were acceptable. The LLOQs were 10 ng/mL for arecoline and guvacoline, and 100 ng/mL for arecaidine. The validated method was successfully applied for a toxicokinetic study in rats, and plasma concentration-time profiles of all analytes were characterized. These results show that the developed method is suitable for the quantitative determination of arecoline, arecaidine, and guvacoline in plasma and can be used in toxicokinetic and pharmacokinetic studies.

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