An HPLC–MS/MS method for the simultaneous determination of luteolin and its major metabolites in rat plasma and its application to a pharmacokinetic study

Abstract

A selective and accurate HPLC-MS/MS method was established to simultaneously quantify luteolin and its active metabolites (diosmetin, chryseriol, and luteolin-7-O-glucuronide) in rat plasma. The analytes were separated on a C column with a mobile phase of water containing 0.5% formic acid and acetonitrile under gradient elution to shorten the total chromatographic run time and increase the resolution of diosmetin and chryseriol. A triple quadruple mass spectrometer coupled with an electrospray ionization source in the negative ion mode was used to detect the analytes. The multiple reaction monitoring transitions were of m/z 284.9→132.9 for luteolin, m/z 298.9→283.9 for diosmetin and chryseriol, m/z 461.1→284.9 for luteolin-7-O-glucuronide, and m/z 300.9→150.9 for the internal standard. The method was linear within the concentration ranges of 0.06-90 μg/mL for luteolin, 0.03-12 μg/mL for diosmetin, 0.015-4.8 μg/mL for chryseriol, and 0.06-60 μg/mL for luteolin-7-O-glucuronide. The intra- and interday precisions were all within 6.0%. Accuracy ranged from -3.2 to 6.4%. The matrix effect and instability were not observed during bioanalysis. This method was used to study the pharmacokinetic characteristics of luteolin and its metabolites in rats after treatment with luteolin.

Pharmacokinetic Comparisons of Different Combinations of Yigan Jiangzhi Formula in Rats: Simultaneous Determination of Fourteen Components by UPLC-MS/MS

“…Meanwhile, a bimodal phenomenon of 3 flavonoids (daidzein, apigenin, and luteolin) was presented in Figure 4. In accordance with what had been reported previously [36][37][38], the first peak appeared in less than 1 h and the second peak at about 5 h or even later probably due to distribution, reabsorption, and enterohepatic circulation [39][40][41].…”

Reparative Effects of Ethanol-Induced Intestinal Barrier Injury by Flavonoid Luteolin via MAPK/NF-κB/MLCK and Nrf2 Signaling Pathways

“…Luteolin and its metabolites can be efficiently absorbed and show bioactivity after oral administration in rats and humans. − In Dong’s study, the quantitative study of rat plasma revealed 3.04 ± 0.60 μg/mL (8.52–12.72 μmol/L) after taking 56.49 mg/kg luteolin . Correspondingly, the rat plasma luteolin concentration of 5–100 μmol/L requires oral administration of 33.27–444.01 mg/kg luteolin.…”

Simultaneous detection of four flavonoids and two alkaloids in rat plasma by LC–MS/MS and its application to a comparative study of the pharmacokinetics between Abri Herba and Abri mollis Herba extract after oral administration

“…MRM scanning mode was used on account of the great advantage in selectivity for the quantification of analytes. In the full scan mass spectra, the quasi‐molecular ions [M+H]+ (hypaphorine and abrine) and [M‐H]‐ (schaftoside, isoschaftoside, isoliquiritigenin and luteolin) were stable and in high abundance, and most of them were in good agreement with the literature data . Thus the [M+H]+ and [M‐H]‐ ions were chosen as the precursor ions for MS/MS fragmentation analysis.…”