PMID- 23643543 OWN - NLM STAT- MEDLINE DCOM- 20140107 LR - 20130528 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 148 IP - 1 DP - 2013 Jun 21 TI - Pharmacokinetic study of four flavones of Glycyrrhiza in rat plasma using HPLC-MS. PG - 266-70 LID - S0378-8741(13)00277-8 [pii] LID - 10.1016/j.jep.2013.04.024 [doi] AB - AIM OF THE STUDY: This study aimed to develop a specific HPLC-MS method for simultaneous quantification of four flavones of Glycyrrhiza in rat plasma after oral administration and to describe the pharmacokinetics of four flavones in rat plasma. MATERIALS AND METHODS: A simple, sensitive and selective method for simultaneous determination of four flavones of Glycyrrhiza in rat plasma, i.e., liquiritin, isoliquiritin, liquiritigenin, and isoliquiritigenin, by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS) with negative electrospray ionization mode, was developed and validated. The method was applied to investigate the pharmacokinetics of four flavones in rat plasma after oral administration of Glycyrrhiza flavones. Chromatographic separation was accomplished on an Agilent TC-C18 column (4.6mmx250mm, and 5mum), with gradient elution by using a mixture of methanoic acid (A) and acetonitrile (B) as the mobile phase at a flow rate of 0.8mL/min. RESULTS: The calibration curves for four flavones had good linearity higher than 0.997 in the measured range. Relative standard deviations (RSDs) of the intra- and inter-day precision at different levels were all less than 4.8%. The pharmacokinetic profile of four flavones in rat plasma was fitted with a two-compartment model detected by a simple, rapid and accurate HPLC-MS method. Time (h) to reach peak concentration (mug/mL) of liquiritin (2.69+/-0.04), isoliquiritin (10.16+/-0.02), liquiritigenin (2.83+/-0.02), and isoliquiritigenin (0.28+/-0.01) was 2.02+/-0.23, 1.97+/-0.20, 0.48+/-0.02, and 1.93+/-0.36, respectively. The distribution and elimination half-life (h) and area under the concentration-time curve (mug/mL-h) from t=0 to last time of liquiritin, isoliquiritin, liquiritigenin, and isoliquiritigenin were 1.02+/-0.48/2.27+/-0.53/16.97+/-0.43, 2.04+/-1.01/2.38+/-0.80/69.20+/-5.24, 0.35+/-0.10/4.26+/-0.16/14.83+/-0.11, and 1.18+/-0.32/3.04+/-0.22/2.10+/-0.09, respectively. Isoliquiritin presented the phenomenon of double peaks and the others appeared together in a single and plateau absorption phase. Isoliquiritigenin had the lowest oral bioavailability because of Cmax and AUC0-infinity. Liquiritigenin had the fastest absorption and distribution rate and the lowest elimination rate according to Tmax, t1/2alpha, and t1/2beta. CONCLUSIONS: This paper first reported on identification and determination of four flavones of Glycyrrhiza in rat plasma and their respective pharmacokinetic characteristics. The results provided a meaningful basis for better understanding the absorption mechanism of Glycyrrhiza and evaluating the clinical application of this medicine. CI - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved. FAU - Wu, Yin-Ping AU - Wu YP AD - School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China. FAU - Meng, Xian-Sheng AU - Meng XS FAU - Bao, Yong-Rui AU - Bao YR FAU - Wang, Shuai AU - Wang S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130430 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Flavones) SB - IM MH - Animals MH - Chromatography, High Pressure Liquid MH - Flavones/blood/*pharmacokinetics MH - *Glycyrrhiza MH - Mass Spectrometry MH - Plant Roots MH - Rats MH - Rats, Sprague-Dawley EDAT- 2013/05/07 06:00 MHDA- 2014/01/08 06:00 CRDT- 2013/05/07 06:00 PHST- 2012/10/23 00:00 [received] PHST- 2013/04/12 00:00 [revised] PHST- 2013/04/13 00:00 [accepted] PHST- 2013/05/07 06:00 [entrez] PHST- 2013/05/07 06:00 [pubmed] PHST- 2014/01/08 06:00 [medline] AID - S0378-8741(13)00277-8 [pii] AID - 10.1016/j.jep.2013.04.024 [doi] PST - ppublish SO - J Ethnopharmacol. 2013 Jun 21;148(1):266-70. doi: 10.1016/j.jep.2013.04.024. Epub 2013 Apr 30.