PMID- 25922266 OWN - NLM STAT- MEDLINE DCOM- 20160427 LR - 20240229 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 169 DP - 2015 Jul 1 TI - An LC-MS/MS method for simultaneous determination of three Polygala saponin hydrolysates in rat plasma and its application to a pharmacokinetic study. PG - 401-6 LID - S0378-8741(15)00299-8 [pii] LID - 10.1016/j.jep.2015.04.033 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Radix Polygala has a long history of use as a sedative in traditional Chinese medicine and its major ingredients are saponins, which are recognized effective in memory improvement but highly toxic to gastricintestinal mucosa. Polygala saponin hydrolysates (PSH), an alkaline hydrolysis product and also the intestinal metabolites of the saponins, exhibited stronger effects in improving memory of mice and had less toxicity than its original saponins. The present study aims to develop a sensitive LC-MS/MS method for simultaneously determining PSH three major active components, 3,4,5-trimethoxycinnamylic acid (TMCA), p-methoxycinnamylic acid (PMCA) and tenuifolin (TF), in rat plasma and apply the method to a pharmacokinetic study. MATERIALS AND METHODS: The acidic plasma (100mul) was treated by liquid-liquid extraction with ethyl acetate and reconstituted sample was analyzed on a C18 column eluted with acetonitrile-water (50:50) containing 0.2% formic acid at 0.4ml/min. The mass detection in negative electrospray ionization was used. The ion pairs for multiple reaction monitoring were set at m/z 237.0/103.0, 177.0/116.6 and 679.5/425.3 for TMCA, PMCA and TF, respectively. Their pharmacokinetic profiles were studied in rats after intravenous and oral dose of PSH at 20 and 100mg/kg, respectively. RESULTS: The calibration curves had good linearity (r(2)>0.99) for TMCA, PMCA and TF within the tested concentration ranges. The limits of detection and quantification were 1, 10, 0.5ng/ml and 10.0, 20.0, 1.0ng/ml, respectively. The intra-day and inter-day precisions were less than 18.9% and accuracies between 93.2% and 113.3%, and the extraction recovery ranged from 91.2% to 112.1% for all analytes. The pharmacokinetic study showed that TMCA, PMCA and TF could be rapidly absorbed into the circulation and reached their peak concentrations at about 9.1, 9.0 and 24.0min, respectively. TF had a lower oral bioavailability (2.0%) than TMCA (90.1%) and PMCA (96.5%), but it remained in the body much longer (t1/2, lambdaz, 4.8h, oral dose) than TMCA (0.6h) and PMCA (0.9h). CONCLUSIONS: A sensitive LC-MS/MS method was developed and applied to a pharmacokinetic study of TMCA, PMCA and TF of PSH in rats. The three components are proved to be bio-available active components of PSH and might display their in vivo pharmacological activities at different levels and different time periods after oral administration. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Wang, Qian AU - Wang Q AD - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China. FAU - Xiao, Bing-Xin AU - Xiao BX AD - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China. FAU - Pan, Rui-Le AU - Pan RL AD - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China. FAU - Liu, Xin-Min AU - Liu XM AD - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China. FAU - Liao, Yong-Hong AU - Liao YH AD - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China. FAU - Feng, Li AU - Feng L AD - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China. FAU - Cao, Fang-Rui AU - Cao FR AD - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China. FAU - Chang, Qi AU - Chang Q AD - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China. Electronic address: qchang@implad.ac.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150425 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - C9096D920O (3,4,5-trimethoxycinnamic acid) RN - 0 (Cinnamates) RN - 0 (Saponins) RN - 0 (tenuifolic saponin) SB - IM MH - Animals MH - Male MH - Rats MH - Chromatography, High Pressure Liquid MH - Cinnamates/blood MH - *Polygala/chemistry MH - *Saponins/blood/chemistry/pharmacokinetics MH - Tandem Mass Spectrometry OTO - NOTNLM OT - Bioavailability OT - Glycyrrhizin acid (PubChem CID: 14982) OT - Hydrolysates OT - LC-MS/MS OT - Pharmacokinetics OT - Polygala saponins OT - Tenuifolin (PubChem CID: 71307577) OT - p-Methoxycinnamylic acid (PubChem CID: 699414) EDAT- 2015/04/30 06:00 MHDA- 2016/04/27 06:00 CRDT- 2015/04/30 06:00 PHST- 2014/12/01 00:00 [received] PHST- 2015/04/12 00:00 [revised] PHST- 2015/04/18 00:00 [accepted] PHST- 2015/04/30 06:00 [entrez] PHST- 2015/04/30 06:00 [pubmed] PHST- 2016/04/27 06:00 [medline] AID - S0378-8741(15)00299-8 [pii] AID - 10.1016/j.jep.2015.04.033 [doi] PST - ppublish SO - J Ethnopharmacol. 2015 Jul 1;169:401-6. doi: 10.1016/j.jep.2015.04.033. Epub 2015 Apr 25.