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??Chrysanthemum morifolium has a long history of culture and use in China. Due to different germplasm resources, producing areas, and processing methods, many cultivated varieties have formed now. The varieties and processing methods of C. morifolium are affected by economic interests and processing cost, which change gradually. On the basis of spot investigation and related literature study, the changes of the varieties and processing methods of C. morifolium were summarized in this paper. It will provide theoretical evidence for the culture, processing, quality evaluation, and clinical application of C. morifolium.     

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??OBJECTIVE To study the monthly dynamics of physical and chemical indexes in Achyranthis Bidentatae Radix(ABR, the dried root of Achyranthes bidentata Bl.) stored in simple and cool warehouses. METHODS ABR was stored in simple and cool warehouses for 27 months. The color was observed. The water content was determined based on the drying method. The contents of ??-ecdysone and 5-hydroxymethylfurfural (5-HMF) were determined by HPLC method. The accumulation of temperature difference between the simple and cool warehouses was evaluated with a relative temperature cumulation (RTC) method. The monthly dynamics of physical and chemical indexes of ABR was analyzed with RTC. RESULTS As the extension of storage time, the ABR stored in the simple warehouse showed deeper color and harder texture, but the ABR stored in the cool warehouse still had soft texture without significant color change. The contents of ??-ecdysone in ABR stored in the two warehouses both gradually decreased and dropped to lower than the limit of 0.030% ruled by China Pharmacopoeia when being stored for up to 27 months. The contents of 5-HMF of ABR stored in the two warehouses both increased and were higher for the sample in the simple warehouse than that in the cool warehouse. CONCLUSION The concept of RTC is put forward and used to study the monthly dynamics of chemical constituents in traditional Chinese medicine during storage for the first time. The physical and chemical indexes of ABR varies during storage. Two years of storage time of ABR is suggested.     

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??OBJECTIVE To discuss the problem of instrumental test method of clarity and degree of opalescence of liquids in the general notice 0902 of China Pharmacopeia(Ch.P)2015, find out the causes and offer solutions. METHODS The test methods of clarity in Ch.P 2015 and European Pharmacopeia (EP) 8.0 were compared, including instrumental types, applicability, sample requirements, and result evaluation. RESULTS The primary opalescent suspension for the instrumental method is the same as the visual method, using the absorbance (A=0.12-0.15) at 550 nm to control the opalescence. Because the resolving power of the instrumental method is far higher than the visual method, the limit becomes interval distribution instead of simple point. The opalescent value (NTU) of the upper limit (A=0.15) is about 1.35 times of the lower limit (A=0.12).When the NTU value of the test liquid is in this interval, the result evaluation will be hard.CONCLUSION The preparation of the primary opalescent suspension in Ch.P 2015 is different from EP8.0. For this reason, the limit set by Ch.P 2015 is actually stricter than that of EP8.0. The opalescent value of the standard solution used by Ch.P 2015 is about 75% of that used by EP8.0.     

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??OBJECTIVE To determine the optimum ultrasonic-assisted extracting process of total flavonoids from Zingiber mioga by response surface methodology, and then study the antioxidant activity of the extract. METHODS On the basis of single factor experiments, a 4-factor, 3-level Box-Behnken center-united experiment was conducted. The Box-Behnken experiment analyzed and optimized the processing conditions by response surface methodology, then the antioxidant activity of the extract was determined. RESULTS The optimum conditions at ultrasonic power of 300 W were as follows treatment temperature 60 ??, ethanol concentration 85.99%, liquid-to-solid ratio 98.08 mL??g^-1, treatment time 15 min. Under the optimum conditions, the extraction rate of the total flavonoids was 37.01%, with a bias of 4.28% compared with the predicted value of 35.49%; the reducing power of the total flavonoids from Zingiber mioga at the concentration of 1.038 7 mg??mL^-1 was equal to that of vitamin C of 56.60 ??g??mL^-1; the ??OH radical scavenging ratio of the total flavonoids from Zingiber mioga was 73.07%, the DPPH radical scavenging ratio was 65.72%, and the inhibition rate of anti-lipid peroxidation was 49.94%. CONCLUSION The total flavonoids from Zingiber mioga can be developed as a new type of antioxidant agents, and regression analysis and parameter optimization of the extracting process can be conducted by using response surface methodology.     

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??OBJECTIVE To develop an LC-MS/MS method for the determination of vonoprazan pyroglutamate and vonoprazan fumarate in rat urine to determince the urine excretion of the two drugs in SD rats. METHODS The detection was performed on an API 4000 tandem mass spectrometer equipped with an electrospray ionization (ESI) source. Multiple reaction monitoring (MRM) was selected with the transitions of m/z 346.2 to 315.2 for TAK-438 P and m/z 237.2 to 194 for IS, respectively. Separation of the analytes was achieved by a Shimadzu liquid chromatography system with an Agelient C₁₈ analytical column (4.6 mm??150 mm, 3.5 ??m). Isocratic elution was adopted with mobile phase A (10 mmol??L^-1 ammonium acetate and 0.1% formic acid) and mobile phase B (methanol) at the ratio of 40??60, at a flow rate of 0.6 mL??min^-1. The total run time was 6 min and the injected sample volume was 5 ??L. All the features of the developed method suggested it met the criteria for bioanalytical METHODS recommended by regulatory authorities. The accumulative urine excretion rates of TAK-438 F and TAK-438 P were determined after oral administration of TAK-438 P and equimolar TAK-438 F in SD rats.RESULTS The accumulative urine excretion rates of the prototype drugs were 2.11% and 2.03%, respectively. The low excretion rates indicated that metabolism might be the major clearance mechanism of TAK-438 P and TAK-438 F. CONCLUSION This was the first time to establish and validate a simple, rapid and sensitive LC-MS/MS method for the quantification of TAK-438 P. There is no significant difference of the accumulative urine excretion rate between TAK-438 P and TAK-438 F in SD rats, which provides the basis for the druggability of TAK-438 P.     

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??OBJECTIVE To design and synthesize a series of oleanolic acid analogs posessing anti-tumor activity based on survivin target. METHODS Using the techniques of computer-aided drug design, the docking of Survivin and known active small molecules was simulated and then the key amino acid residue fragment of the target protein was analyzed. It led to the discovery of active groups capable of binding to the critical sites. Through using the natural product, oleanolic acid, as a lead compound, the active groups were introduced onto its A-ring, and the carboxyl group at the C-28 position was modified using amidation. SGC-7901 and A549 cells were used to screen the antitumor activity in vitro through the standard MTT method. RESULTS Ten new oleanolic acid derivatives were designed and synthesized,and their structures were confirmed by MS and NMR. The compounds ??₅ and ??₅ exhibited more potent cytotoxicity than the positive control drugs. CONCLUSION The novel oleanolic acid analogues have better antitumor activity than the parent compound, which are worthy of further study.     

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??OBJECTIVE To design and synthesize brain targeting danshensu (DSS) derivatives and study their metabolism in rat plasma and brain homogenate in vitro. METHODS Tetramethylpyrazine and its derivatives were selected as carriers to design the brain targeting danshen suderivatives. Lipid-water partition coefficient (logP), brain blood concentration ratio (BB), and P-glycoprotein affinity of the derivatives were predicted by some calculation softwares and the better compound DT3 was chosen for the next synthesis. The degradation of DT3 and its intermediate DT1 in rat plasma and brain homogenate were measured by HPLC-UV. RESULTS Two danshensu-pyrazine ester derivatives were synthesized, ie DT1 and DT3. A simultaneous determination method of DT3, DT1, and (3,5,6-trimethylpyrazine-2-yl)methanol (TMPM) in rat plasma and brain homogenate was established. The degradation of DT3 in rat plasma and brain homogenate underwent the following processDT3??DT1??the active metabolites of DSS and TMPM.Compared with DT1, the degradation of DT3 in rat plasma slowed down.The half-lives (t_1/2) of TMPM were 1.68 and 1.71 min, respectively. Also,DT3 could quickly release the active metabolitein rat brain homogenate, and the concentration of TMPM showed a steady increase with a t_1/2 of 222.88 min. CONCLUSION The danshensu-pyrazine ester derivative DT3 has an extended t_1/2 in rat plasma, and it can be degraded to active metabolite quickly in rat brain homogenate.     

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??OBJECTIVE To evaluate the bioequivalence of cefdinir suspension and reference cefdinir capsule in Chinese healthy male subjects.METHODS A single oral dose of 100 mg cefdinir suspension or cefdinir capsule was given to 24 subjects according to a 2-way crossover design. The plasma concentrations of cefdinir were determined by UPLC-MS/MS. The pharmacokinetic parameters were calculated and bioequivalence was compared by WinNonlin 6.3 program. RESULTS The main pharmacokinetic parameters of cefdinir suspension and cefdinir capsule were as follow: ??_max were (1 034.78??358.17), (969.71??297.38) ng??mL^-1;t_max were (2.98??0.60), (3.44??0.70) h; AUC_0-12 were (4 911.24??1 675.30), (4 522.35??1 600.13) ng??h??mL^-1; AUC_0-?? were (5 026.24??1 735.32),(4 680.69??1 699.93) ng??h??mL^-1;t_1/2 were (1.71??0.23), (1.79??0.39) h. The 90% confidential interval of ??_max, AUC_0-12, AUC_0-?? of tested formulation were 95.6%-115.3%, 99.9%-117.2%, 99.0%-116.0%. CONCLUSION The two formulations are bioequivalent.     

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??OBJECTIVE To prepare ion-sensitive ophthalmic in situ gel containing bendazac lysine (BDZL-ISG) and preliminarily study its rheological behavior, in vitro drug release, corneal permeation, and pharmacokinetics in rabbit aqueous humor. METHODS Single factor investigation was carried out to optimize the formulation, taking viscosity and gelling capacity as evaluation indices. Using aqueous solution or eye drops as control, the in vitro release of the formulation was evaluated by dialysis membrane method. Then, the corneal permeation experiment of the optimum formulation was carried out with Franz diffusion cell. The pharmacokinetics of BDZL-ISG in rabbit aqueous humor was preliminarily studied by microdialysis. RESULTS Compared with the control group, the optimum formulation had shear thinning behavior and significant sustained release effect. There was no significant difference in the corneal permeation between the two groups. The RESULTS of pharmacokinetic study showed that ??_max (13.25 ??g??L^-1) and AUC_0-t of BZDL-ISG were 2.38 and 2.2 times higher than those of BDZL eye drops respectively, which suggested that the ocular bioavailability of BDZL was greatly enhanced by the optimum in situ gel formulation. CONCLUSION With significant sustained release effect, the ion-sensitive ophthalmic in situ gel will become a promising alterative formulation for bendazac lysine for treatment of cataracts.     

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??OBJECTIVE To establish the HPLC fingerprints of Feijiehe pills and provide a foundation for its quality control and evaluation. METHODS A gradient elution method was applied. Ten batches of samples were analyzed by HPLC on a Diamonsil C₁₈ (4.6 mm??250 mm,5 ??m) column with mobile phase composed of acetonitrile-0.01% phosphoric acid solution at a flow rate of 0.8 mL??min^-1, the detection was carried out at 270 nm, and the column temperature was maintained at 25 ??. RESULTS There were 10 common peaks in the HPLC fingerprints. The similarity between peaks was more than 0.90. CONCLUSION The method is simple, accurate, reliable, and suitable to be applied to the quality control of Feijiehe pills.     

荆芥内酯在大鼠体内的排泄研究

 目的 研究荆芥内酯在大鼠体内的排泄情况。方法 建立液-液萃取后HPLC测定大鼠尿液、粪便和胆汁中荆芥内酯含量的方法,并对大鼠灌胃/静脉注射荆芥内酯后的排泄情况和排泄特点进行分析。结果 大鼠灌胃荆芥内酯（24 mg·kg^-1）后,胆汁12 h内、尿液36 h内的排泄具有明显的雌雄差异（P0.05）;静脉注射荆芥内酯（12 mg·kg^-1）后,尿液36 h内的排泄具有明显的雌雄差异（P0.05）。结论 荆芥内酯在大鼠尿液和胆汁中的排泄具有明显的雌性差异,以原型形式随尿液、粪便和胆汁排泄的量很少,可能主要以代谢产物的形式排出体外。     

柠檬苦素在大鼠体内的排泄途径分析

目的:考察柠檬苦素在大鼠体内的代谢途径,为阐明该药物的作用机制提供参考。方法:大鼠按80 mg·kg~(-1)灌胃给予柠檬苦素,收集胆汁、尿液和粪便,利用HPLC和LC-MS/MS测定大鼠胆汁、尿液和粪便中柠檬苦素的含量,计算其累积排泄量和累积排泄分数。结果:柠檬苦素在大鼠粪便、尿液和胆汁中的累积排泄分数合计约50%,只有近一半的药物以原型形式排泄出体外。原药从尿液和胆汁中的总排泄量1%,大部分以原型药物通过粪便排出。结论:柠檬苦素在大鼠体内的主要排泄途径为粪便,少量药物吸收进入血液后通过肝脏代谢,少量药物通过尿液排出体外。     

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??OBJECTIVE To identify the metabolites of Pulsatilla oleanolic acid 3-??-L-rhamnopyranosyl (1??2) -??-L-pyran arabinoside (B7) in rat plasma, bile, urine, feces, and in vitro liver microsomes incubation system. METHODS An ultra-high performance liquid chromatography combined with electrospray ionization quadrupole time of flight mass spectrometry (UHPLC-Q-TOF-MS) method was developed and successfully applied to the study on the metabolites of B7 in rat plasma, bile, urine, feces, and in vitro liver microsomes incubation system after oral administration. RESULTS A total of 23 metabolites were identified, of which 12 metabolites were present in rat liver microsomes incubation system. CONCLUSION Deglycosylation, demethylation glucuronidation, and hydroxylation are the major metabolic transformation forms of B7 in rats in vivo and in vitro.     

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??OBJECTIVE To identify the metabolites of Flos scabiosae extract in rats after oral administration for exploring its metabolism mode in vivo. METHODS Welch Ultimate UHPLC C₁₈ column (2.1 mm??100 mm, 1.7 ??m) was used for the analysis, and the column temperature was maintained at 25 ??. Gradient elution was conducted with mobile phase consisting of 0.1% acetic acid water (A) and acetonitrile (B) at a flowing rate of 0.35 mL??min^-1. The injection volume was 6 ??L. Urine, plasma, and feces samples were collected during 0-24 h or 0-12 h after oral administration of Flos scabiosae extract to rats.The samples and control samples were analyzed by UHPLC-Q-T MS/MS in the scanning mode to acquire the full-scan chromatograms. The data acquisition and processing analysis were conducted using compound retention time, precise molecular mass, elemental composition, isotopic abundance, and mass spectra with Peak View v1.2 data processing software. Metabolites were identified by comparison of chromatograms of the urine, feces and plasma samples after administraion of Flos scabiosae extract with those of the blank biological samples and the herb extract.RESULTS The developed method is applicable to the analysis and identification of metabolites of Flos scabiosae extract in biological matrices after oral administration. Based on the investigation of Flos scabiosae extract in rats, 28 parent compounds with 31 metabolites were detected in rat urine, feces, and plasma. CONCLUSION In this study, the developed method is simple and efficient. The main metabolism pathways of Flos scabiosae extract in rats may include oxidation, demethylation, glucuronidation, and sulfation. This study provides a novel pattern and illumination for the research of material basis of Flos scabiosae.     

羟基红花黄色素A脂质载体及水溶液在大鼠体内的代谢、排泄、生物利用度研究

目的：研究不同的羟基红花黄色素A（HSYA）剂型对HSYA代谢、排泄、生物利用度的影响。方法：大鼠灌胃给予HSYA脂质制剂和水溶液,采用HPLC及LC-MS检测血浆、胆汁、粪便、尿液样品。结果：大鼠灌胃给予HSYA脂质制剂和水溶液后,在大鼠胆汁中均发现HSYA及其II相代谢产物;HSYA原药的质荷比为611,而两个II相代谢产物的质荷比分别为918和691,结合酶降解实验表明这两个代谢产物分别为HSYA的谷胱甘肽结合物和硫酸酯结合物。但是同水溶液相比,HSYA脂质制剂显著性降低了HSYA及其II相代谢产物从胆汁的排泄量。大鼠灌胃给予HSYA脂质制剂后,HSYA原药从胆汁、粪便、尿液中24h的累积排泄量分别为（0.05±0.03）%、（8.80±2.30）%、（37.99±17.50）%,其cmax、AUC0-8h分别为2.79μg·mL^-1、402.51μg·min·mL^-1;而大鼠灌胃给予HSYA水溶液后,HSYA原药从胆汁、粪便、尿液中24h的累积排泄量分别为（0.32±0.22）%、（44.66±8.00）%、（5.58±1.30）%,其cmax、AUC0-8h分别为0.08μg·mL^-1、10.73μg·min·mL^-1。结论：实验结果表明脂质制剂可能不会改变HSYA的代谢机制,但是显著性降低了HSYA从粪便和胆汁的排泄量,提高了其生物利用度。     

基于超高效液相色谱-四极杆飞行时间质谱技术的洋川芎内酯H在大鼠体内的代谢产物分析

目的 采用超高效液相色谱-四极杆飞行时间质谱(UHPLC-Q-TOF-MS)技术对洋川芎内酯 H 在大鼠体内的代谢产物进行分析鉴定。方法 SD大鼠灌胃给药后,收集其血浆、尿液、胆汁和粪便,并对样品进行前处理。采用ThermoAccucore C₁₈色谱柱(2.1 mm×150 mm,2.6 μm),以体积分数0.1%乙酸-水(A相)-乙腈(B相)作为流动相进行梯度洗脱。根据准分子离子峰和碎片离子信息,结合对照品与文献报道,对大鼠血浆、尿液、胆汁和粪便中的原型成分及其代谢产物进行鉴定。结果 最终在大鼠血浆、尿液、胆汁和粪便中共检测到32个代谢产物,包括24个Ⅰ相和8个Ⅱ相代谢物。结论 洋川芎内酯 H 主要的体内代谢反应包括氧化、氢化、去羟基化、甲基化、葡萄糖醛酸化、硫酸酯化、半胱氨酸结合、谷氨酰胺结合以及相关的复合反应等。本研究应用高分辨液质联用技术阐明了洋川芎内酯 H 在大鼠体内的代谢产物,为今后药效学和药理学研究奠定了基础。     

大鼠口服红花水提物和红花黄色素后羟基红花黄色素A的排泄研究

建立简便的高效液相色谱法(HPLC)测定大鼠口服红花水提物和红花黄色素后尿、粪和胆汁中主要活性成分羟基红花黄色素A(HSYA)的含量。色谱柱为Hypersil BDS-C18(250×4．6mm,5μm),流动相为乙腈-0．3%冰醋酸水溶液梯度洗脱,检测波长320nm,葛根素或对羟基苯甲醛为内标。尿、粪和胆汁中的HSYA的日内精密度小于3．1%,日间精密度小于5．8%。提取回收率为79．2%～102．1%。该方法首次研究了大鼠口服红花水提物和红花黄色素后羟基红花黄色素A的排泄情况。     

伪人参皂苷GQ的排泄试验研究

目的:研究大鼠舌下静脉给药伪人参皂苷GQ后,其在胆汁、粪和尿中的排泄情况。方法:采用高效液相-蒸发光散射色谱(HPLC-ELSD)法测定大鼠胆汁、粪和尿中伪人参皂苷GQ,Diamonsil C₁₈色谱柱(4.6 mm×250mm,5μm),以甲醇-水(24∶7)为流动相,流速1.0 mL.min^-1,检测温度为50℃,灵敏度为10,以氮气为载气,压力为303 975 Pa。结果:HPLC-ELSD测定方法的标准曲线线性关系、样品回收率和日内、日间精密度均符合要求。伪人参皂苷GQ大鼠舌下静脉给药后,主要以胆汁排泄为主,占总药量的41.60%;其次为粪排泄,占总药量的9.97%;尿液中仅检出少量伪人参皂苷GQ。结论:大鼠胆汁、粪和尿中主要以伪人参皂苷GQ原形药物排泄。     

20(S)-原人参二醇奥克梯隆型差向异构体大鼠排泄研究

20（S）-原人参二醇奥克梯隆型差向异构体为20（S）-原人参二醇的主要代谢产物,前期研究发现,该差向异构体在药效学和药动学方面均有一定的立体选择性。该文建立了HPLC-MS/MS测定大鼠尿液、粪便和胆汁中的24R-差向异构体和24S-差向异构体,考察口服灌胃给予大鼠24R-差向异构体或24S-差向异构体后,在尿液、粪便和胆汁中的排泄情况。结果显示,24R-差向异构体和24S-差向异构体在口服给药后48 h内粪便排泄累积量分别为给药剂量的17.69%,17.09%,基本不经尿排泄。口服给药后48 h内,24R-差向异构体和24S-差向异构体胆汁排泄累积量分别为给药剂量的8.01%,1.47%,前者是后者的5.4倍,具有明显的立体选择性。