LC-MS/MS determination and pharmacokinetic study of seven flavonoids in rat plasma after oral administration of Cirsium japonicum DC. extract

Ethnopharmacological relevance: Cirsium japonicum DC, a Traditional Chinese Medicine, has the curative effect of antihemorrhagic and antitumor. Pharmacological studies prove that the curative effect may relate to the flavonoids. A simple and rapid resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was first developed and validated for the quantification of seven flavonoids including pectolinarin, linarin, pectolinarigenin, hispidulin, diosmetin, acacetin and apigenin in rat plasma after oral administration of Cirsium japonicum DC extract Materials and methods: The chromatographic separation was achieved on a C-18 column with gradient elution by using a mixture of 0.1% formic acid aqueous solution and methanol as the mobile phase at a flow rate of 0.8 mL/min. A tandem mass spectrometric detection was conducted using multiple-reaction monitoring (MRM) via an electrospray ionization (ESI) source in positive and negative ionization mode simultaneously. Samples were pre-treated by a single-step protein precipitation with methanol, and sulfamethoxazole was used as internal standard (IS). Results: The optimized mass transition ion-pairs (m/z) for quantization were 623.4/3152 for pectolinarin, 593.3/285.1 for linarin, 315.3/3002 for pectolinarigenin, 301.2/286.2 for hispidulin, 301.2/2582 for diosmetin, 283.0/267.9 for acacetin, 269.0/117.0 for apigenin and 2522/155.8 for IS. After oral administration of 6 mL/kg Cirsium japonicum DC extract in rats, the maximum plasma concentration (C-max) of pectolinarin, linarin, pectolinarigenin, hispidulin, diosmetin, acacetin and apigenin were 876.77 +/- 97.34 ng/mL, 86.79 +/- 1.70 ng/mL, 6.13 +/- 0.12 ng/mL, 32.85 +/- 2.50 ng/mL, 37.2 +/- 2.04 ng/mL, 19.02 +/- 1.29 ng/mL and 14826 +/- 20.63 ng/mL, respectively. The time to reach the maximum plasma concentration (T-max) was 5 min for pectolinarin, linarin, pectolinarigenin, hispidulin, diosmetin, acacetin and 360 mm for apigenin. The intra-day and inter-day precisions (RSD%) for seven compounds were less than 13.16% and 7.77% and the accuracy (RE%) range from -7.92% to 14.77%. Conclusions: This is the first research on the pharmacokinetic study of bioactive components in rat plasma after oral administration of Cirsium japonicum DC extract The results provided a meaningful basis for better understanding the absorption mechanism of Cirsium japonicum DC and evaluating the clinical application of this herb medicine. (C) 2014 Elsevier Ireland Ltd. All rights reserved.