The simultaneous determination of naringenin and its valine carbamate prodrug in rat plasma using supercritical fluid chromatography -tandem mass spectrometric method.

ABSTRACT

To enhance the oral bioavailability of naringenin, a valine carbamate prodrug was firstly synthesized. It is essential to measure naringenin and its carbamate prodrug simultaneously for evaluating their pharmacokinetic behavior in Sprague-Dawley rats. Here, the samples were analyzed by a supercritical fluid chromatography-tandem mass spectrometric (SFC-MS/MS) method after extracting by liquid-liquid extraction with ethyl acetate. The analytes were eluted completely on an ACQUITY UPC2TM BEH 2-EP column (3.0 × 100 mm, 1.7 µm) within 2.5 min by gradient elution. The mass transition ion pairs were m/z 273.2→153.0, 416.0→153.1, and 271.2→91.0 for naringenin, the prodrug, and genistein (the internal standard), respectively. Naringenin and the prodrug had excellent linear correlations over the range of 2-1000 ng/mL (r > 0.995) and 4-2000 ng/mL (r > 0.998), with lower limits of quantification of 2 ng/mL and 4 ng/mL, respectively. The intra-day and inter-day precision and accuracy for all quality control samples were within ± 15 %. The high-throughput, sensitive, and economical SFC-MS/MS method was successfully applied to the pharmacokinetic study of naringenin and its carbamate prodrug for the first time. The pharmacokinetic study results showed the total Cmax of naringenin in prodrug group was 4.14-fold higher than naringenin group. The higher total AUC value observed with prodrug group indicated increased bioavailability of naringenin as compared to naringenin suspension. The present work provides some helpful information for future studies of naringenin and its carbamate prodrug.