Ethnopharmacological relevance: Cistanche tubulosa (Schrenk) R. Wight (Orobanchaceae) is a frequently prescribed component in many traditional herbal prescriptions which are used to treat diabetes in China. In recent studies, the antidiabetic activity of Cistanche tubulosa extracts have been confirmed. However, no systematic investigation has been reported on the total glycosides of Cistatnche tubulosa (TGCT). Aim of the study: The present study aimed to investigate the hypoglycemic and hypolipidemic effects of TGCT and the potential mechanisms in diet/streptozotocin (STZ)-induced diabetic rats, and to chemically characterize the main constituents of TGCT. Materials and methods: The major constituents of TGCT were characterized by HPLC/Q-TOF-MS and the analytical quantification was performed with HPLC-DAD. Type 2 diabetic rats were induced by high-fat highsucrose diet (HFSD) and a single injection of STZ (30 mg/kg). TGCT (50 mg/kg, 100 mg/kg and 200 mg/kg) or metformin (200 mg/kg) were orally administered for 6 weeks. Body weight and calorie intake were monitored throughout the experiment. Fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), area under curve of glucose (AUC-G), glycosylated hemoglobin (HbA1c), fasting insulin, serum C-peptide, glycogen content and insulin sensitivity index were tested. The levels of phosphorylated protein kinase B and phosphorylated glycogen synthase kinase 313, the activities of hexokinase and pyruvate kinase were assayed. Meanwhile, the changes in serum lipid profiles, superoxide dismutase, glutathione peroxidase, malondialdehyde and inflammatory factors were measured. Histological of pancreas were also evaluated by haematoxylin-eosin stain. Results: Our investigation revealed the presence of phenylethanoid glycosides (PhGs): echinacoside (500.19 +/- 11.52 mg/g), acteoside (19.13 +/- 1.44 mg/g) and isoacteoside (141.82 +/- 5.78 mg/g) in TGCT. Pharmacological tests indicated that TGCT significantly reversed STZ-induced weight loss (11.1%, 200 mg/kg); decreased FPG (56.4%, 200 mg/kg) and HbA1c (37.4%, 200 mg/kg); ameliorated the OGTT, AUC-G and insulin sensitivity; increased glycogen content (40.8% in liver and 52.6% in muscle, 200 mg/kg) and the activities of carbohydrate metabolizing enzymes; regulated lipid profile changes and the activities of antioxidant enzymes; diminished serum markers of oxidative stress and inflammation in a dose-dependent manner (p < 0.05). Conclusions: This study confirmed that TGCT was an effective nutritional agent for ameliorating hyperglycemia and hyperlipidemia in diet/STZ-induced diabetic rats, which might be largely attributed to the activities of TGCT on inhibitions of oxidative stress and inflammation.

Seven undescribed labdane diterpenoids, japonicones A-G, were isolated from the aerial parts of Leonurus japonicus Houtt. Japonicones C-G contained two keto carbonyl groups in their structures attached to C-3 and C-7, which are rare for labdane diterpenoids. The structures and absolute configurations of japonicones A-G were established by means of spectroscopic analyses (HRESIMS, 1D and 2D NMR, and ECD). Their anti-inflammatory activities were evaluated by measuring their inhibitory effects on PGE2 production in LPS-stimulated RAW264.7 macrophages. Japonicones A-D and G showed inhibition of PGE2 production with IC50 values in the range of 8.62-30.71 μM (the positive control paracetamol showed an IC50 = 5.79 μM).

目的 建立电感耦合等离子体质谱(ICP-MS)法测定银怡片(骨碎补、葛根、D-氨基葡萄糖硫酸钾盐等)中Ca、As、Hg、Pb的含有量.方法 样品经微波消解后,ICP-MS法测定元素含有量,内标法改善基体效应及干扰.条件为等离子体体积流量15 L/min;雾化气体积流量0.90 L/min;辅助气体积流量1.2 L/min;ICP射频功率1.5 kW;脉冲阶段电压1 300 V,模拟阶段电压-2 000 V.结果 4种元素在各自范围内线性关系良好(r≥0.998 2),平均加样回收率83.1％～100.6％,RSD＜4％.结论 该方法灵敏准确,分析速度快,可用于银怡片的质量控制.

目的 建立高效液相-蒸发光散射检测器(HPLC-ELSD)法同时测定银怡片(骨碎补、葛根、D-氨基葡萄糖硫酸钾盐等)中氨基葡萄糖、硫酸软骨素的含有量.方法 该药物水提液的分析采用Waters Xbridge Amide色谱柱(酰胺柱,4.6 mm× 150 mm,3.5 μm),以乙腈-50 mmol/L乙酸铵(含0.6％三乙胺)为流动相,等度洗脱(75∶25);体积流量0.8 mL/min;柱温40℃;蒸发光散射检测器,漂移管温度105℃;载气N2,体积流量2.5 mL/min.结果 氨基葡萄糖盐酸盐、硫酸软骨素钠分别在0.172 5～0.689 9 mg/mL (r=0.999 9)、0.168 7～0.674 7 mg/mL (r=0.999 4)范围内呈良好的线性关系,平均加样回收率分别为95.19％、103.72％,RSD分别为1.14％、2.84％.结论 该方法简便灵敏,重复性好,可用于银怡片的质量控制.

As an important integral part of traditional Chinese medicine chemical biology( TCMCB),it is of great importance to rapid isolate,and reliably identify the chemical components in herbal medicines. Phytochemical studies on the anti-inflammatory active part of Chinese dragon's blood,the red resin of Dracaena cochinchinensis,resulted in the isolation of two compounds,nordracophane( 1) and dracophane( 2),using LC-MS and chromatographic techniques( Silica gel,ODS and preparative HPLC). The structures,cyclic dihydrochalcane trimers,were elucidated on the basis of 1 D and 2 D NMR,MS,IR and UV spectral analysis. Compound 1 is a new compound,and 2 is isolated from D. cochinchinensis for the first time. Both compounds exhibited significant inhibition of nitric oxide production in lipopolysaccharides( LPS)-stimulated RAW264. 7 cells with IC50 values of( 14. 9±4. 50) and( 9. 0±0. 7) μmol·L-1.

目的 研究中药复方热毒宁注射液解热抗炎活性部位的化学成分.方法 采用脂多糖(LPS)诱导小鼠内毒素休克模型对热毒宁注射液解热抗炎活性部位进行筛选,综合应用HP-20大孔树脂、硅胶、MCI、ODS柱色谱以及反相MPLC、HPLC等各种现代色谱技术对解热抗炎活性部位进行系统的分离纯化,根据化合物的光谱数据和理化性质进行结构鉴定.采用LPS诱导小鼠巨噬细胞RAW264.7模型,以抑制炎性细胞因子前列腺素E2(PGE2)的分泌为评价指标对分离得到的化合物进行体外抗炎活性评价.结果 热毒宁注射液经大孔吸附树脂95％乙醇洗脱部位为解热抗炎活性部位,从中分离得到了24个化合物,分别鉴定为(4aS,7aS,7bS)-4,4a,7a,7b-tetrahydro-2H-1,7-dioxacyclopent[cd]indene-5-carboxylic acid methyl ester(1)、(4aS,7aS)-1,4a,5,7a-tetrahydro-7-(hydroxymethyl)-cyclopenta[c]pyran-4-carboxylic acid methyl ester(2)、3α,5α-tetrahydrodeoxycordifoline lactam(3)、R-(Z)-4-甲基-5-[(2',6',6'-三甲基-4'-氧代-2'-环己烯-1'-基)亚甲基]-2(5H)-呋喃酮(4)、(1α,2α,3β,4β)-2,4-双(4-羟基-3-甲氧基苯基)-1,3-环丁烷二甲酸(5)、4-[(6-O-苯甲酰基-β-D-吡喃葡萄糖基)氧基]-3-甲氧基苯甲酸(6)、丁香脂素(7)、E-3-(3,4-二羟基苯亚甲基)-5-(3,4-二羟基苯基)二氢呋喃-2-酮(8)、6,7-二甲氧基香豆素(9)、7-羟基-6-甲氧基香豆素(10)、水杨酸(11)、丁香醛(12)、苯乙酸(13)、香草醛(14)、咖啡酸(15)香草乙酮(16)、3,5-O-二咖啡酰奎宁酸(17)、4,5-O-二咖啡酰奎宁酸(18)、3,4-O-二咖啡酰奎宁酸甲酯(19)、3,5-O-二咖啡酰奎宁酸甲酯(20)、4,5-O-二咖啡酰奎宁酸甲酯(21)、5-O-咖啡酰奎宁酸乙酯(22)、3,5-O-二咖啡酰奎宁酸乙酯(23)、4,5-O-二咖啡酰奎宁酸乙酯(24).其中化合物1、10、14～24对LPS诱导的RAW264.7细胞中PGE2的分泌具有显著的抑制作用.结论 化合物1～9、11～13、22～24均为首次从热毒宁注射液中分离得到,有机酸类化合物可能为热毒宁注射液解热抗炎的主要药效物质基础之一.

The study aims to qualitatively analyze the chemical composition of compound Nanxing acesodyne plaster by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS). The analysis was performed on Agilent Zorbax SB-C_(18)( 4. 6 mm×250 mm,5 μm) column. The mobile phase consisted of methanol and 0. 2% formic acid-water was used as gradient elution. The flow rate was 1 mL·min~(-1) and column temperature was 30 ℃. The Mass spectrometry was acquired in both positive and negative ion modes using ESI. The components were identified by the precise mass-to-charge ratio,secondary fragmentation and other information combined with reference substance and literature data. As a result,58 compounds were identified and predicted,including alkaloids,flavonoids,coumarins,organic acids and lactone compounds,of which 12 compounds were verified by the reference substances. The results provide reference for the quality control of compound Nanxing acesodyne plaster,and lay the foundation for elucidating the active components mechanism.

目的:建立采用1H定量核磁共振波谱法测定二对甲苯磺酸缘生替尼对照品的含量.方法:采用核磁共振波谱法.使用Bruker AscendTM 400超导核磁共振谱仪,以氘代DMSO为溶剂,脉冲宽度为10.0μs,延迟时间为1s和扫描次数32的条件下采集试样氢谱.结果:以化学位移δ分别为5.31和6.28的二对甲苯磺酸缘生替尼和顺丁烯二酸的氢质子峰作为定量峰,其峰面积比与其质量比的线性回归方程为Y=0.128 1X-0.000 4,相关系数为0.999 9,含量测定的重复性试验的RSD为0.20％(n=6).测得二对甲苯磺酸缘生替尼的含量为98.54％.结论:分析结果表明,在没有对照品的情况下,核磁共振波谱法可用于二对甲苯磺酸缘生替尼的含量测定,该方法可行,具有快速、准确、简便的优点.

目的 建立桂枝茯苓胶囊(GFC)中三萜酸类成分UPLC/Q-TOF-MS指纹图谱方法,为评价GFC的质量提供新方法.方法 采用UPLC分离三萜酸类成分,用Q-TOF-MS检测,建立UPLC/Q-TOF-MS指纹图谱.结果 得到灵敏度、选择性和专属性良好的GFC中三萜酸类成分UPLC/Q-TOF-MS指纹图谱,确定了26个共有峰,其中3、5～18、20、23、24共18个峰来自于茯苓,2号峰来自于白芍和牡丹皮,4号峰来自于茯苓、牡丹皮、白芍、桂枝,19号峰来自于牡丹皮、白芍和桂枝,21号峰来自于牡丹皮和白芍,22、25号峰来自于茯苓、牡丹皮、桃仁、白芍、桂枝,26号峰来自于桂枝、白芍、桃仁.10批GFC指纹图谱相似度在0.90以上.UPLC-Q-TOF-MS共鉴定出16个成分,分别为16α-羟基松苓新酸、16α-羟基-栓菌酸、3-酮基-6,16α-二羟基-羊毛甾-7,9(11),24-三烯-21酸、去氢土莫酸、土莫酸、3-酮基-6,16α-二羟基-羊毛甾-8,24-二烯-21酸、依布里酸、猪苓酸C、3-表去氢土莫酸、3-O-乙酰基-16α-羟基松苓新酸、3-表去氢茯苓酸、3-O-乙酰基-16α-羟基-栓菌酸、去氢茯苓酸、茯苓酸、松苓新酸、去氢齿孔酸.结论 该方法准确、快速,具有较好的精密度、重复性和稳定性,适用于GFC的质量控制.

目的:采用在线中心切割超高效二维液相色谱(2D-UPLC)法,建立同时测定复方南星止痛膏中3个双酯型乌头生物碱(新乌头碱、乌头碱和次乌头碱)的含量测定方法.方法:一维UPLC采用Waters XBridgeBEH C18色谱柱(2.1 mm×50 mm 1.7 μm),以甲醇-0.008％二乙胺为流动相,梯度洗脱,流速0.1 mL· min-1,柱温18℃;二维UPLC采用Waters XBridge BEH C18色谱柱(3.0 mm×100 mm 1.7 μm),以乙腈-0.01％磷酸为流动相,梯度洗脱,流速0.7 mL· min-1,柱温40℃.进样量1μL,检测波长235 nm.结果:新乌头碱、乌头碱和次乌头碱的线性范围分别为0.66～9.90、0.55～8.20和0.91～13.72 μg· mL-1,R2分别为0.999 5、0.999 9和0.999 6,线性关系良好;3个成分的平均加样回收率在82.5％～88.8％之间,方法的准确度和稳定性均较好;复方南星止痛膏中新乌头碱、乌头碱和次乌头碱含量分别在3.2～5.0、0.9～1.3、8.5～10.4 μg· g-1范围内.结论:该方法有效改善了复方南星止痛膏中待测组分的分离度,极大提高了检测灵敏度,对制剂中的3个双酯型乌头生物碱进行准确定量分析,提高产品的质量控制水平,并为临床用药提供理论支持.

Ginkgo diterpene lactone (GDL) is the raw material for ginkgo diterpene lactone meglumine injection, which is used for treating cerebral ischemia. The aims of this study were to explore the cellular pharmacokinetics of GDL in whole cells and subcellular fractions, and detect cellular pharmacodynamics on the human SH-SY5Y cells induced by oxygen-glucose deprivation and reoxygenation (OGD/R). Firstly, a simple, sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for assessing the amount of ginkgolide A (GA), B (GB) and K (GK) in cellular/subcellular samples. Then, phosphatidylserine and mitochondria membrane potential were assayed to evaluate the extent of apoptosis effect. The study showed that the cellular/subcellular accumulation of GA and GB were increased in a concentration-dependent manner; the levels of GA and GB in cytosol were the highest among these subcellular organelles. Meanwhile, GDL also attenuated the OGD/R-induced increases in the percentage of apoptotic and mitochondria membrane potential. In addition, verapamil increased the rate and amount of GA and GB entering cellular/subcellular compartments through inhibition of P-glycoprotein activity, and promoted the protective effect of GDL. The present study reports the cellular pharmacokinetics profiles of GA and GB in normal and OGD/R-induced SH-SY5Y cells in vitro for the first time, which provided valuable information for clinical safety application.

ETHNOPHARMACOLOGICAL RELEVANCE:Gardenia jasminoides fruit (GJF) is used as a well-known traditional folk medicine, a food and a natural colorant in Asia with a long history. The herbal medicine has usually been harvested in the autumn from September to November. However, this time span is too long and might result in the quality instability of GJF.AIM OF STUDY:We aimed to conduct the comprehensive quality evaluation of GJF including the quantitative analysis of the bioactive components and the main bioactivities, and further to determine the most appropriate harvest time of this phytomedicine.MATERIALS AND METHODS:In this study, an UFLC-Q-TRAP-MS/MS method was established to quantify 7 iridoid glycosides (geniposide, geniposidic acid, secoxyloganin, gardenoside, genipin 1-gentiobioside, scandoside methyl ester, and shanzhiside), 7 phenylpropanoid acids (chlorogenic acid, cryptochlorogenic acid, neochlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, isochlorogenic acid C, and caffeic acid) and 2 carotenoids (crocin-1 and crocin-2) in GJF. With this method, nine samples of GJF harvested at different times were analyzed and compared. These samples were also investigated and compared in terms of their antioxidant activity (DPPH free radical scavenging, ABTS free radical scavenging, ferric-reducing antioxidation) and anti-influenza activity (neuraminidase inhibition), which are closely related to the GJF efficacies. Then, hierarchical cluster analysis (HCA) was separately performed for the quantitative analysis and bioactivity evaluation in vitro.RESULTS:The HCA results demonstrated that three GJF samples (S5, S6, and S7) were clustered into one group for both quantitative analysis and bioactivity evaluation in vitro; these three samples were found to have the highest standardized scores in both the former (12.775, 12.106, 10.817) and the latter (3.406, 3.374, 3.440). Based on the comprehensive results, the optimum harvest period was confirmed to extend from mid-October to early-November.CONCLUSIONS:This study firstly validated the use of UFLC-Q-TRAP-MS/MS method for the determination of 16 bioactive components in GJF. It was also the first time that a quantitative analysis and a bioactivity assay in vitro were integrated for the determination of the most appropriate harvest period of GJF. We hope this paper may provide some reference to studies of appropriate harvest periods and even the quality control of TCMs.

Ten fractions(A-J) were prepared by separation of Longxue Tongluo Capsules(LTC) by using silica gel column chromatography and orthogonal experimental design,showing similar chemical profiles with different abundances of peaks.These ten samples were assessed with UHPLC-QE OrbitrapHRMS for 97 common peaks.For the pharmacological activity experiment,three kinds of in vitro cell models including lipopolysaccharide(LPS)-induced BV-2 microglial cells NO release model,oxygen-glucose deprivation/reoxygenation(OGD/R)-treated HUVEC vascular endothelial cells injury model,and OGD/R-treated PC-12 nerve cells injury model were employed to evaluated the bioactivity of each fraction.Based on the contribution of each identified component,grey relation analysis and partial least squares(PLS) analysis were performed to establish component-activity relationship of LTC,identify the potential active components.After that,validation of the potential active components in LTC was carried out by using the same models.The results indicated that 4 phenolic compounds including 7,4'-dihydroxyhomoisoflavanone,loureirin C,4,4'-dihydroxy-2,6-dimethoxydihydrochalcone,and homoisosocotrin-4'-ol,might be the active components for anti-neuroinflammation effect;five phenolic compounds such as 3,5,7,4'-tetrahydroxyhomoisoflavanone,loureirin D,7,4'-dihydroxyhomoisoflavane,and 5,7-dihydroxy-4'-methoxy-8-methyflavane,might have positive effects on the vascular endothelial injury;three phenolic compounds including 5,7,4'-trihydroxyflavanone,7,4'-dihydroxy-5-methoxyhomoisoflavane,and loureirin D,might be the active components in LTC against neuronal injury.

银杏已有600多年的药用历史.历代中医药文献大多认为银杏有毒或有小毒.大量的临床试验均表明银杏类制剂具有较好的耐受性.多数不良反应如过敏反应、自发性出血、癫痫发作等多散见于个案报道.虽然动物毒理学试验发现银杏类制剂具有致癌性,细胞毒理学试验发现某些黄酮苷类如槲皮素、山柰酚具有基因毒性,但大量的临床和流行病学研究尚未发现银杏类制剂或其中的成分与癌症具有相关性.与抗血小板、抗凝药物、精神神经类药物、钙离子拮抗剂等联用时,要注意药物之间的相互作用引发的不良反应.企业应发挥不良反应监测的主体作用,积极构建药物上市后安全性证据体.本文对银杏类制剂的安全性研究进行综述,以期为临床应用和进一步开发此类制剂提供参考.

Hyperlipidemia is a major component of metabolic syndrome, and regarded as one of the main risk factors causing metabolic diseases. We have developed a therapeutic drug, akebia saponin D (ASD), and determined its anti-hyperlipidemia activity and the potential mechanism(s) of action by analyzing the metabolome and intestinal microbiota. Male Sprague-Dawley rats were fed a high fat diet to induce hyperlipidemia, and then given ASD orally for 8 weeks. Lipid levels in serum were determined biochemically. Metabolites in serum, urine and feces were analyzed by UPLC-Q/TOF-MS, and the structure of the intestinal microbiota was determined by 16S rRNA sequencing. The ASD treatment significantly decreased the levels of TC, TG and LDL-c and increased the serum level of HDL-c. Metabolomics analysis indicated that the ASD treatment mainly impacted seven differential metabolites in the serum, sixteen differential metabolites in the urine and four differential metabolites in feces compared to the model group. The ASD treatment significantly changed eight bacteria at the genus level compared to the model group. In conclusion, ASD treatment can significantly alleviate HFD-induced hyperlipidemia and the hypolipidemic effect of ASD treatment is certainly associated with a systematic change in the metabolism, as well as dynamic changes in the structure of the intestinal microbiota.

Stroke has become the second leading cause of death in the world, and the most common type is the ischemic stroke. Due to its rapid onset and complex conditions, ischemic stroke is a major neurological disorder that causes disability. Ischemic stroke mainly results from atherosclerosis, and the pathogenesis of ischemic stroke mainly includes energy metabolism disorders in the brain, the toxicity of excitatory amino acids, oxidative/nitrification stress, inflammatory response, apoptosis, and autophagy. With the characteristics of multi-component and multi-target, traditional Chinese medicine could be used to treat ischemic stroke at different stages. This article summarized the latest research progress on the pathogenesis of ischemic stroke and commonly used traditional Chinese medicine for treatment of ischemic stroke in order to provide references for the further research and clinical treatment of ischemic stroke.

目的研究建立辛紫通鼻颗粒的高效液相色谱多波长融合指纹图谱分析方法,为辛紫通鼻颗粒的质量控制提供依据.方法色谱柱为Waters Symmetry C18(4.6 mm×250mm,5μm);混合流动相:流动相A为乙腈、流动相B为0.15 moL·L-1磷酸二氢钠水溶液,梯度洗脱,检测波长250 nm、280 nm、327 nm,柱温26℃.结果建立了辛紫通鼻颗粒指纹图谱,标示出15个共有峰,10批样品相似度均在0.987～0.998之间.结论:建立的多波长融合指纹图谱可用于辛紫通鼻颗粒的质量控制.

To observe the protective effect of Longxue Tongluo capsule (LTC) on human umbilical vein endothelial cells (EAhy.926 cells) injury induced by oxidized low-density lipoprotein (ox-LDL, 100 mg·L⁻¹). The effect of the cell viability of LTCin alleviating OX-LDL-induced endothelial cell injury was determined by MTT and LDH assay. The effect of LTC on lactic dehydrogenase (LDH), nitric oxide (NO), super oxide dlsmutase (SOD) and malondialdehyde (MDA) levels were detected by corresponding assay kits according to manufacturer's instruction. The effect of LTC on the protein expressions of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), p65, p-p65, IKB and p-IKB were detected by Western blot. The results showed that compared with the normal control group, the activity of EAhy.926 cells was significantly decreased, LDH leakage (P<0.01) increased, NO content and SOD activity significantly decreased (P<0.01, P<0.05), and the expressions of ICAM-1, VCAM-1, p-p65/p65 and p-IKB(P<0.05)increased.This study demonstrated that LTC had no significant effect on the growth of normal cells. The treatment with LTC significantly promoted the proliferation of vascular endothelial cells damagedby ox-LDL, decreased MDA content and LDH release, andincreased the activity of SOD and NO content. Meanwhile, ox-LDL significantly increased the expressions of ICAM-1, VCAM-1, p-p65/p65, p-IKB/IKB in Eahy.926 cells; these effects were suppressed by LTC at 1, 2 mg·L⁻¹. In conclusion, LTC has a significant protective effect on human umbilical vein endothelial cells caused by ox-LDL. This study suggested that LTC has a certain therapeutic effect on AS.

Although wide applications towards ischemic stroke in clinic, the therapeutic materials of Longxuetongluo Capsule (LTC) that is composed of total phenolic extract of Chinese dragon's blood, are still largely unclear. Exposure pattern characterization of those drug-derived components in vivo, notably in circulation system has been recommended as a viable approach to disclose the effective components of a given herbal medicine. Herein, we aimed to develop a robust method being capable of multi-component quantification in either rat plasma or tissues following oral administration of LTC, and to clarify the kinetic profiles of 11 primary drug-derived phenolic derivatives. Proteins precipitation was carried out for the plasma as well as homogenized tissue samples with acetonitrile. Chromatographic separations were achieved using UHPLC equipped with a shim-pack XR-ODS II column, and confidence-enhanced detection was accomplished through the joint employment of selected-reaction monitoring and tandem mass spectrometry (SRM-MS/MS) on a hybrid triple quadrupole-linear ion trap mass spectrometer. Diverse validation assays proved the method to be sensitive, precise, and rapid for simultaneous determination of those 11 components. Pharmacokinetic and tissue distribution investigations were subsequently conducted in rat after a single 500 mg/kg oral dose. Rapid absorption (T-max,11.53-68.27 min) and elimination (T-1/2, 6.893-57.90 min) occurred for all analytes-of-interest. Extensive occurrences were observed for 7,4'-dihydroxy-5-methoxyhomoisoflavanone (C-max, 340.0 ng/mL), thevetiafiavone (C-max, 42.86 ng/mL), 5,7,4'-trihydroxyhomoisoflavanone (C-max, 41.55 ng/mL), and pterostilbene (C-max, 25.49 ng/mL) in plasma. Significant distributions occurred for all analytes in the liver as well as kidney, and several compounds could be found in brain. The findings described are envisioned to provide promising information for the in-depth clarification of the therapeutic entities, and also to offer a practical approach for therapeutic drug monitoring of LTC in clinic. (C) 2018 Elsevier B.V. All rights reserved.

In this study, an effective method was developed for the isolation and enrichment of Ginkgo biloba extract by continuous chromatography system. The adsorption and desorption ratio of flavonoids as main index, the best macroporous resin was screened out from six resins by static adsorption and desorption tests. At the same time the adsorption and desorption parameters were optimized by dynamic adsorption and desorption tests. Under optimal parameters, five operations consisting of loading, washing, desorbing, regenerating, and balancing were integrated across the continuous chromatography system for the purpose of refining 66 L of crude extract solution. The results were as follows, 198.22 g of Ginkgo biloba extracts was produced, which contained 65.83 g of flavonoids and 15.44 g of lactones. The content of flavonoids and lactones increased from 2.76 and 0.72% in the crude extract to 33.21 and 7.79%, with a recovery yield of 91.26 and 81.21%. Methodology validation showed that the proposed method had high stability and reproducibility. Compared with the traditional macroporous resin method, the proposed method had a short processing time and low solvent consumption. Our studies indicated that the newly developed method is an effective procedure for the isolation and enrichment of Ginkgo biloba extract.