ICP-MS法测定不同产地红参中9种无机元素

目的 考察不同产地红参中铁（Fe）、锰（Mn）、锌（Zn）、铜（Cu）、硒（Se）、铅（Pb）、砷（As）、汞（Hg）和镉（Cd）9种无机元素的含量差异。方法 采用微波消解技术及电感耦合等离子体质谱（ICP-MS）法测定28批不同产地红参中9种无机元素含量,并采用SPSS 22.0软件进行聚类分析。结果 不同产地红参Fe、Mn、Zn含量均较高,Se含量极低,有害元素Pb、As、Hg、Cd、Cu含量均符合《中国药典》限量标准。28批样品聚类为两类。结论 不同产地红参均富含Fe、Mn、Zn,其重金属及有害元素污染程度小,安全性相对较好。不同产地红参Fe、Zn、Cu、Se、As元素含量差异性均较小,Mn、Pb、Hg、Cd元素差异性较大。     

ICP-MS同时测定骨折挫伤胶囊中重金属的含量

目的 建立测定骨折挫伤胶囊中铅（Pb）、镉（Cd）、铜(Cu)、砷（As）、汞(Hg)元素含量的电感耦合等离子体-质谱（ICP-MS）法。方法 样品经人工胃液提取,以锗（Ge）、铟（In）、铋（Bi）为内标,采用ICP-MS法同时测定5种元素。结果 5种元素质量浓度在线性范围内与响应强度线性关系良好,平均回收率97.4%～102.7%,RSD均小于3.5%（n=6）。结论 该方法准确,灵敏,无干扰,可用于骨折挫伤胶囊中5种重金属及有害元素的测定。     

广地龙药材、汤剂及配方颗粒的元素分析

摘 要 目的：分析广地龙药材、汤剂及配方颗粒中多种重金属及有害元素,比较三者元素差异。方法: 通过电感耦合等离子体质谱仪（ICP-MS）对广地龙样品中的铬、铜、砷、镉、锡、锑、钡、汞、铅、铋等10种元素进行检测。结果: 大部分广地龙样品的重金属和有害元素,如As、Cd等含量较高,药材样品中8批As含量高于2 mg·kg-1,10批Cd含量高于0.3 mg·kg-1,配方颗粒样品则分别为10批和2批。 结论: 广地龙药材的元素含量直接反映在汤剂及配方颗粒中,应从药材来源保证临床使用安全性,提高现有广地龙药材质量标准,建立配方颗粒质量标准。     

基于生物可给性和靶器官毒性剂量法的乌梢蛇中铅和砷联合暴露评估

目的 通过考察乌梢蛇Zaocys dhumnades（Cantor）中铅（Pb）和砷（As）的生物可给性,并探索靶器官毒性剂量（TTD）法在评估中药中重金属联合暴露风险中的应用,为限量标准的制定提供参考。方法 通过胃-肠两步模拟消化（in vitro PBET）联合电感耦合等离子体质谱（ICP-MS）法对乌梢蛇中Pb和As的生物可给性进行考察,根据其生物可给性计算其日暴露量。采用危害指数（HI）法对于Pb和As联合暴露产生的健康风险进行初步筛查;进一步针对不同毒理学终点,采用TTD法对Pb和As的累积风险进行更加精确的评估。结果 8批乌梢蛇中Pb和As的合格率为100%。HI法的初步评估结果表明,所有批次乌梢蛇中Pb和As的HI值均＜1。TTD法评估结果表明,作用终点心血管系统、神经系统、肾脏、血液和睾丸,所有批次乌梢蛇的HI值均＜1,健康风险可接受。结论 基于生物可给性,探索乌梢蛇中Pb和As的累积风险评估方法,为中药外源性有害残留物风险评估的方法开发提供新的思路,为制定更加科学的限量标准提供技术支撑。     

基于ICP-MS法对4种动物源性药材中16种无机元素的测定及量变规律研究

目的 测定地龙、土鳖虫、九香虫、蜂房4种动物源性药材中无机元素,并探索其元素量变规律。方法 采用微波消解法对样品进行前处理,电感耦合等离子体质谱（ICP-MS）法对地龙、土鳖虫、九香虫、蜂房中铍（Be）、钒（V）、钴（Co）、镍（Ni）、镓（Ga）、硒（Se）、铷（Rb）、锶（Sr）、银（Ag）、铯（Cs）、铀（U）、铜（Cu）、砷（As）、镉（Cd）、汞（Hg）和铅（Pb）16种无机元素进行测定,并采用元素指纹图谱直观分析、元素主成分分析、偏最小二乘判别分析、聚类分析对元素含量差异性进行统计分析。结果 16种无机元素的线性关系良好（R>0.996）,回收率为87.4～113.0%。4种动物药中检测了16种无机元素含量,并绘制无机元素指纹图谱,发现其谱图具有一定的特征性,4种动物药中As、Cd和Pb残留量较高,有害无机元素的量超标应引起关注。通过主成分分析、偏最小二乘法判别分析、聚类分析,发现不同样品元素之间含量变异均能呈现出明显特征,并以此可区分不同种类的动物药。结论 通过无机元素在4种动物药中的组成分布及其量的变化规律研究,为动物药的质量控制及安全性评价提供依据,同时为动物药重金属形态价态研究提供基础参考。     

人参等10种中药材及饮片中重金属及有害元素测定

目的：采用微波消解-电感耦合等离子体质谱（ICP-MS）法测定人参、白茅根、白头翁、苍术、大黄、骨碎补、苦参、龙胆、红参、肉苁蓉10种中药材及饮片中重金属及有害元素的含量。方法：采用微波消解法对样品进行前处理,电感耦合等离子体质谱（ICP-MS）法对500批中药材及饮片中铅、镉、砷、汞、铜5种重金属及有害元素进行含量测定,并对样品中镍、铬、钡3种金属元素含量进行考察,应用SPSS19.0软件对数据结果进行统计学分析。结果：同一品种8种元素测定值与来源（野外采集、基地种植与市售饮片）及产地无明显相关性。500批样本测定结果显示：铅、镉、砷、汞、铜元素总超标率分别为6.60%、25.20%、1.00%、0.00%、0.40%;元素残留量与药材品种存在一定的相关性,镉元素在白头翁、苍术、骨碎补、龙胆药材中容易蓄积,而铅元素易在白头翁药材中蓄积残留,导致残留量较高。大黄、白头翁、龙胆中钡元素、镍元素、铬元素含量均明显高于其他品种。汞均未超出0.2 mg·kg^-1;除5批样本外,砷均未超出2 mg·kg^-1;除2批样本外,铜均未超出20 mg·kg^-1,表明上述10种中药材及饮片中砷、汞、铜元素残留方面的安全隐患较低。结论：有必要对中药材及饮片中部分重金属元素的含量加以监管,以保证中药的品质和临床用药安全。该方法准确、简便、灵敏,可为中药材及饮片中重金属及有害元素的检测与控制提供参考。     

ICP-MS分析丽水地产灵芝中的重金属元素

目的 采用电感耦合等离子体质谱法（ICP-MS）建立灵芝中砷（As）、汞（Hg）、铅（Pb）、镉（Cd）、铜（Cu）5种重金属元素的测定方法。方法 采用微波消解仪进行消解,以¹¹⁵In、⁷²Ge、²⁰⁹Bi为内标,采用ICP-MS法测定丽水产地灵芝的菌盖与菌柄中As、Hg、Pb、Cd、Cu的含量。结果 检测的5种元素线性关系良好,相关系数r ≥ 0.999 1。22批样品中Cd超出限度的有5批,As、Pb超出限度的各有1批,Cu超出限度的有2批。Cu、Cd、Hg在菌盖中的富集较多,As、Pb则在菌柄中富集较明显。结论 该方法灵敏、高效、准确,且分别测定了灵芝不同药用部位的重金属含量,对龙泉灵芝栽培基地选择,人工种植过程中重金属含量控制等具有现实意义,可用于灵芝的安全性评价。     

电感耦合等离子体-质谱法测定注射用益气复脉（冻干）中的22种无机元素

目的 采用电感耦合等离子体-质谱（ICP-MS）法建立注射用益气复脉（冻干）中22种无机元素的含量测定方法。方法 以微波消解法处理样品,硝酸为消解试剂,样品经微波消解后,采用电感耦合等离子体质谱仪测定注射用益气复脉（冻干）中22种无机元素（Li、B、Mg、Al、Si、S、Ti、V、Cr、Fe、Ni、Co、Zn、Ga、As、Sr、Mo、Cd、Sb、Ba、Ce、Pb）的量,并进行专属性、线性关系、精密度、重复性、回收率考察;完成6批制剂中22种元素测定并评价其安全性。结果 建立22种元素标准曲线,确定检出限及定量限,方法学验证均符合要求。6批供试品中已检出元素含量均远低于安全限值,对产品质量不会造成安全风险。结论 该方法简便、快速、准确,可用于测定注射用益气复脉（冻干）中22种元素的含量,为其质量控制、安全性评价提供一定参考。     

微波消解-电感耦合等离子体质谱法测定动物类中药中的5种有害元素

摘 要 目的：建立微波消解 电感耦合等离子体质谱法（ICP MS）测定动物类中药中的Pb、Cd、As、Hg、Cu等5种有害元素的方法。方法: 样品经HNO3 H2O2微波消解后,优化了电感耦合等离子体质谱仪工作参数,基体干扰和质谱干扰分别通过使用Ge、In、Bi内标溶液和碰撞反应池技术（KED模式）消除。结果: 5种有害元素的检出限在0.04～0.52 μg·L-1,方法精密度（RSD）为1.1%～4.8%,回收率为92.4%～110.0%。利用本方法对40批次的动物类中药中的5种有害元素进行了测定,结果表明某些动物类中药的有害元素含量较高。结论: 本方法快速灵敏准确,适用于动物类中药中的有害元素的分析。     

电感耦合等离子体质谱法测定甘草中铅、镉、砷、汞、铜含量的不确定度评定

摘 要 目的：建立电感耦合等离子体质谱法（ICP MS）测定甘草中铅（Pb）、镉（Cd）、砷（As）、汞（Hg）、铜（Cu）含量不确定度的方法。方法: 用ICP MS法测定甘草Pb、Cd、As、Hg、Cu的含量,通过对测定方法流程进行分析,确定不确定度来源,并计算合成测量不确定度。结果: 甘草中Pb、Cd、As、Hg、Cu的扩展不确定度分别为0.114 2, 0.046 2, 0.069 6,0.029 2, 1.061 8 mg·kg^-1。结论:该方法通过分析各分量的标准不确定度的大小来优化实验,使测定结果更加准确可靠,适用于ICP MS法测定甘草中重金属及有害元素的不确定度评定,并为此类不确定度的评定提供重要参考。     

Synthesis and evaluation of 2,6-piperidinedione derivatives as potentially novel compounds with analgesic and other CNS activities

New 2,6-piperidinediones 2_a–g and 4_a–d were prepared by initial condensation of aromatic aldehydes or cycloalkanones with cyanoacetamide to give α-cyanocinnamides l_a–g or cycloalkylidenes 3_a,b which underwent Michae1 addition with ethyl cyanoacetate or diethylmalonate. Compounds 4_a–d were alkylated by various alkyl halides to produce the N-alkylated 2,6-piperidinedione derivatives 5_a–m. Some new selected compounds 2_a–c,f, 4_a–d & 5_e,h,j were pharmacologically evaluated for potential anticonvulsant, sedative and analgesic activities. These compounds exhibited significant anticonvulsant and analgesic effects after a single I.P. administration 100 mg/kg b.wt. . On the other hand all the investigated compounds induced hypnotic activity and prolonged the phenobarbital sodium- induced sleep as compared with the control group and the most potent compound was found to be 2_f.     

Metabolism and hepatotoxicity of N,N-dimethylformamide,N-hydroxymethyl-N-methylformamide,and N-methylformamide in the rat

The metabolism and hepatotoxicity ofN,N-dimethylformamide (DMF) and two of its metabolites,N-hydroxymethyl-N-methylformamide (HMMF) andN-methylformamide (NMF) were evaluated over a 4-day period in rats. DMF toxicity was dose dependent and delayed toxicity after the administration of a high DMF dose (13.7 mmol/kg) in comparison to a lower dose (4.1 mmol/kg) was observed. Treatment of rats with 13.7 mmol/kg DMF, HMMF, or NMF showed i) that DMF is more toxic than HMMF or NMR, and ii) that hepatotoxicity occurs later for DMF than for HMMF or NMF. Analysis of serum and urine samples demonstrated that DMF is first metabolized to HMMF, which is then partially converted to NMF. After HMMF administration, NMF was found both in serum and in urine. The time course of DMF and HMMF toxicity in relation to NMF formation fitted the hypothesis that the hepatotoxicity of DMF and HMMF is mediated via NMF. The degree of hepatotoxicity after HMMF and NMF treatment is similar. However, the degree of DMF hepatotoxicity is much higher than in the case of NMF or HMMF. The role of NMF as an obligatory intermediate in DMF and HMMF hepatotoxicity is discussed.     

去壁灵芝孢子粉片的含量测定与免疫调节及心脏保护功能研究

目的 研究并评价“仙芝3号”去壁灵芝孢子粉片的免疫调节和心脏保护作用。方法 首先运用UPLC-Q-TOFMS和比色法分析“仙芝3号”去壁灵芝孢子粉片的主要化学成分,考察其对斑马鱼巨噬细胞减少症模型、斑马鱼心衰模型、H2O2诱导的心肌及内皮细胞氧化应激模型、脂多糖诱导的小胶质细胞炎症模型的影响,通过巨噬细胞形成能力、巨噬细胞吞噬能力、抗神经炎症能力、心脏收缩舒张改善能力、抗心肌及内皮细胞氧化应激损伤能力等多个指标评估其免疫调节及心脏保护作用。结果 “仙芝3号”去壁灵芝孢子粉片可以提高巨噬细胞形成及吞噬能力,改善心脏收缩舒张功能,减少神经炎症并缓解心肌及内皮细胞因氧化应激而造成的损伤,从而起到免疫调节和心脏保护作用。结论 “仙芝3号”去壁灵芝孢子粉片有望用于免疫功能调节及心脏功能保护。     

Tricalysiolide G and tricalysiols A and B: rearranged ent-kaurane-type and ent-kaurane-type diterpenoids from the leaves of Tricalysia dubia (Lindl.) Ohwi

Three rearranged ent-kaurane diterpenes with the cafestol-type framework have been isolated from the leaves of Tricalysia dubia. Two were found to be known diterpenoids, tricalysiolides B and C. Tricalysiolide B was isolated as colorless prisms in this experiment and its three-dimensional structure was determined by X-ray crystallography. The remaining diterpenoid was a new compound and was named tricalysiolide G. Two new ent-kaurane-type diterpenoids, given the trivial names tricalysiol A and tricalysiol B, were also isolated. The structures of the new compounds were elucidated from spectroscopic evidence.     

Terbinafine susceptibility patterns for onychomycosis-causative dermatophytes and Scopulariopsis brevicaulis

The in vitro antifungal activity of terbinafine against 521 clinical isolates of seven species of dermatophytes, including four onychomycosis-causative species, as well as five Scopulariopsis brevicaulis isolates was determined by a modified Clinical and Laboratory Standards Institute microdilution method. Results showed a high antifungal activity of terbinafine against all dermatophyte isolates (geometric minimal inhibitory concentration (MIC)=0.026 microg/mL; concentration inhibiting 50% of mycological growth (MIC50)=0.03 microg/mL; and concentration inhibiting 90% of mycological growth (MIC90)=0.06 microg/mL). The geometric mean MICs against onychomycosis-causative dermatophyte species was lower (0.024 microg/mL) than the global MIC. However, the in vitro activity of terbinafine against S. brevicaulis was considerably lower (geometric mean MIC=1.38 microg/mL) in comparison with dermatophytes. The antifungal activity of itraconazole was lower than that of terbinafine against these fungi. These data confirm the high in vitro antifungal activity of terbinafine against dermatophytes, under standardised conditions.     

Prevalence and characterization of the mechanisms of macrolide, lincosamide and streptogramin resistance in viridans group streptococci

The presence of erm genes conferring constitutive and inducible resistance, as well as that of the mefA gene conferring only constitutive resistance, was investigated using PCR in 70 erythromycin resistant (MIC≥1 mg/l) strains of viridans group streptococci (VGS) (18 Streptococcus mitis biotype 1, 16 S. mitis biotype 2, 15 S. oralis, 12 S. salivarius and nine S. sanguis) isolated from the oropharynx of healthy Greek children. All of the 56 isolates belonging to resistance phenotype M harbored the mefA gene. All of the 14 isolates constitutively resistant to macrolides and lincosamides (phenotype CR) harbored the ermB gene. Co-presence of both genes was not observed, whereas class A erm gene (previously known as ermTR) was not detected. Our results are consistent with a possible role of VGS as a reservoir of resistance genes now prevalent in pathogenic species of streptococci.     

Investigation of the prevalence of tetQ, tetX and tetX1 genes in Bacteroides strains with elevated tigecycline minimum inhibitory concentrations

In this study, the antibiotic susceptibilities to tigecycline and tetracycline of 35 selected Bacteroides fragilis group strains were determined by Etest, and the presence of tetQ, tetX, tetX1 and ermF genes was investigated by polymerase chain reaction (PCR). tetQ was detected in all 12 B. fragilis group isolates (100%) exhibiting elevated tigecycline minimum inhibitory concentrations (MICs) (≥8 μg/mL) as well as the 8 strains (100%) with a tigecycline MIC of 4 μg/mL, whilst tetX and tetX1 were present in 15% and 75% of these strains, respectively. All of these strains were fully resistant to tetracycline (MIC ≥ 16 μg/mL). On the other hand, amongst the group of strains with tigecycline MICs < 4 μg/mL (15 isolates), tetQ, tetX and tetX1 were found less frequently (73.3%, 13.3% and 46.7%, respectively). All but two strains harbouring the tetQ gene in this group were non-susceptible to tetracycline, with a MIC > 4 μg/mL. These data suggest that in most cases tigecycline overcomes the tetracycline resistance mechanisms frequently observed in Bacteroides strains. However, the presence of tetX and tetX1 genes in some of the strains exhibiting elevated MICs for tigecycline draws attention to the possible development and spread of resistance to this antibiotic agent amongst Bacteroides strains. The common occurrence of ermF, tetX, tetX1 and tetQ genes together predicted the presence of the CTnDOT-like Bacteroides conjugative transposon in this collection of Bacteroides strains.     

Bioaccessibility of Hg, Cd and As in cooked black scabbard fish and edible crab

Regular consumption of seafood has been widely recommended by authorities. Yet, some species accumulate high levels of contaminants like Hg, Cd and As. In addition, the risks associated to the consumption of such seafood may increase if consumers use cooking practices that enhance the concentration of contaminants and their bioaccessibility. In this study, the bioaccessibility of Hg, Cd and As was assessed with in vitro human digestion of raw and cooked black scabbard fish (Hg; steamed, fried and grilled) and edible crab (Cd and As; steamed and boiled) tissues. Additionally, the toxicological hazards associated with the consumption of these products were also discussed. Generally, Hg, Cd and As bioacessibility increased throughout the digestion process. Cadmium and As revealed high bioaccessibility rates in raw and cooked samples (up to 100%), whereas lower bioaccessible fractions of Hg was observed (up to 40%). Furthermore, this study pointed out the importance of food matrix, elemental chemical properties and cooking practices in the bioaccessibility of Hg, Cd and As. The toxicological hazards revealed that edible crab brown meat (Cd) and grilled black scabbard fish (MeHg) consumption in children should be moderated. In contrast, edible crab muscle (Cd) and fried or steamed black scabbard fish (MeHg) should be consumed to minimize exposure. The use of bioaccessible contaminant data strongly reduced the toxicological risks of MeHg, whereas less risk reduction occurred with Cd and inorganic As.     

Metabolic activation of aromatic and heterocyclicN-hydroxyarylamines by wild-type and mutant recombinant human NAT1 and NAT2 acetyltransferases

Recombinant human NAT1 and polymorphic NAT2 wild-type and mutantN-acetyltransferases (encoded byNAT2 alleles with mutations at 282/857, 191, 282/590, 341/803, 341/481/803, and 341/481) were expressed inEscherichia coli strains XA90 and/or JM105, and tested for their capacity to catalyze the metabolic activation (viaO-acetylation) of theN-hydroxy (N-OH) derivatives of 2-aminofluorene (AF), and the heterocyclic arylamine mutagens 2-amino-3-methylimidazo [4,5-f]quinoline (IQ), 2-amino-3,4-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Both NAT1 and NAT2 (including all mutant human NAT2s tested) catalyzed the metabolic activation of each of theN-hydroxyarylamines to products that bound to DNA. Metabolic activation of N-OH-AF was greater than that of the heterocyclicN-hydroxyarylamines. The relative capacity of NAT1 versus NAT2 to catalyze activation varied withN-hydroxyarylamine substrate. N-OH-MeIQx and N-OH-PhIP exhibited a relative specificity for NAT2. These results provide mechanistic support for a role of the genetic acetylation polymorphism in the metabolic activation of heterocyclic amine mutagens and carcinogens.     

Photodegradation and phototoxicity of thioridazine and chlorpromazine evaluated with chemical analysis and aquatic organisms

The photochemical behaviour of chlorpromazine (CPZ) and thioridazine (THR) incubated under VIS light and a UV-A lamp was investigated with a high-performance liquid chromatography photodiode array detector (HPLC-PAD) and two bioassays. VIS light caused the decrease of CPZ and THR to 25% and 34% of the initial level, respectively, while UV-A degraded the drugs almost totally. CPZ and THR were very toxic to the protozoan Spirostomum ambiguum (Spirotox) and anostracan crustacean Thamnocephalus platyurus (Thamnotoxkit F^TM) with 24-h LC50 values of around 0.5 mg l⁻¹. In spite of the drastic decrease of the concentration of the drugs, the irradiated samples were toxic to the protozoan, especially when a sublethal end-point was taken into consideration. Contrary to the protozoan the crustacean was not sensitive to the products of photodegradation. Mass spectrometry analysis showed the presence of dimers and trimers of the CPZ and mono-, di-, and tri-oxygenated derivatives of THR. The presented data give a strong indication of the importance of the investigation of the environmental fate of drugs, especially those known to be phototoxic.