中成药和保健食品中18种非法添加降压药物的HPLC QTOF/MS定性检测

摘 要 目的：建立降压类中成药和保健食品中非法添加18种降压药物的液相色谱串联四级杆飞行时间质谱（HPLC-QTOF/MS）快速定性检测方法。方法: 采用Agilent Eclipse plusC₁₈(50 mm×2.1 mm,1.8 μm)色谱柱进行分离,以0.5%甲酸水-乙腈为流动相梯度洗脱,流速为0.2 ml·min^-1,离子源为ESI源,正离子检测模式,对降压类中成药及保健品中非法添加的该18种化学药物进行定性检测。结果: 18种化学药物的检出限分别为0.2～2.5 ng·mL^-1,12批供试品中有1批检测到添加了利血平。结论:该方法专属性强、灵敏度高,适用于降压类中成药及保健品中非法添加该18种化学药物的定性分析。     

HPLC同时测定中成药及保健品中添加的16种糖皮质激素

目的 建立一种准确、高效的HPLC同时检测多类中成药及保健品中非法添加的16种糖皮质激素。方法 采用Agilent Extend-C₁₈(250 mm×4.6 mm,5 μm)为色谱柱;乙腈-0.1 mol·L^-1乙酸铵溶液为流动相,梯度洗脱,检测波长为240 nm。结果 16种糖皮质激素在0.2~25 μg·L^-1内线性良好;各成分最低定量限浓度均<0.05 ng·mL^-1;回收率,除了贴膏剂(57.2%~83.8%),其余剂型均获得满意结果(≥78.5%)。结论 本方法简单高效,结果准确可靠,通用性强,可作为同时检测中成药及保健品中非法添加的16种常用糖皮质激素的有效方法。     

液质联用法检查中成药及保健食品非法添加的17种辅助改善记忆类药物

摘 要 目的：建立准确、灵敏的LC MS/MS方法甄别中药制剂及保健食品中可能非法添加的17种辅助改善记忆类药物。方法: 采用液相色谱-串联质谱法（LC-MS/MS）,以Eclipse XDBC₁₈（100 mm×3.0 mm,1.8 μm）为分析柱,以电喷雾电离（ESI）、多反应监测（MRM）扫描方式,对中药制剂及保健食品中非法添加的17种化学成分进行快速定性定量分析。结果: 建立了快速分离检测17种非法添加成分的测定方法,检测限低于10 ng·mL^-1。结论:该方法专属性强、灵敏度高,可用于辅助改善记忆类中药制剂及保健食品中非法添加化学成分的定性和定量分析。     

HPLC法同时测定抗风湿类中成药及保健品中非法添加9种解热镇痛类化学药物

摘 要 目的： 建立抗风湿类中成药及保健品中非法添加9种解热镇痛类化学药物（对乙酰氨基酚、吡罗昔康、萘普生、美洛昔康、芬布芬、尼美舒利、双氯芬酸钠、吲哚美辛、布洛芬）的HPLC测定方法。方法: 色谱柱：Agilent Eclipse XDB-C₁₈(250 mm×4.6 mm,5 μm);流动相:1.8%冰醋酸溶液 乙腈（62∶38）;流速：0.8 ml·min^-1;检测波长：264 nm;柱温：30℃;进样量：20 μl。结果: 9种解热镇痛类化学药物得到良好分离,在测定范围内线性关系良好(r≥0.999 9),检测限为3.6～18.2 ng,定量限为12.0～60.0 ng,平均回收率为98%以上。结论: 该方法专属性好、操作简便、快速准确, 可用于抗风湿类中成药及保健品中非法添加解热镇痛类化学药物的检测。     

降糖保健食品和中成药中12种化学药的液相快速筛查

目的 建立降糖保健食品和中成药中12种化学药的液相快速筛查方法。方法 采用HPLC-DAD,色谱条件：Agilent Extend C₁₈色谱柱(4.6 mm×250 mm,5 μm),以0.014%三氟乙酸水溶液(pH 2.7±0.05)、0.01 mol·L^-1庚烷磺酸钠溶液、乙腈为三元梯度洗脱流动相,柱温：30 ℃,流速：1.0 mL·min^-1,检测波长：220 nm。结果 12种化学降糖药实现了同时分离与专属性鉴别;利用本法从28种39批样品中检出7种12批非法添加化学药品。结论 本法可用于降糖类保健食品及中成药中非法添加12种化学降糖药的快速筛查。     

液质联用法检测镇静安神类中药制剂及保健品中非法掺入的化学品

目的: 建立检测镇静安神类中药制剂和保健品中非法掺入化学品的液质联用方法,并对10批市售样品进行检测。方法: 采用液相色谱-离子阱质谱法,选用C₁₈柱,分别以甲醇-乙腈-0.5%甲酸(15:25:60)和甲醇-水(60:40)为流动相,对样品的提取液进行分析。结果: 在10批受试制剂中,1批被检测出非法掺有地西泮。结论: 该法选择性强,灵敏度高,可以用于分析检测中药制剂及保健品中是否掺入相应化学品。     

UHPLC-MS/MS测定人血浆中的阿普斯特浓度及生物等效性研究

目的 采用超高效液相色谱-串联质谱（UHPLC-MS/MS）法,建立了快速、 简单、 灵敏的测定人血浆中阿普斯特浓度的方法并用于阿普斯特人体生物等效性试验研究。方法 采用蛋白沉淀法处理,以阿普斯特-d5作为内标,色谱柱为Phenomenex Kinetex C₁₈柱(2.1 mm×50 mm, 2.6 µm),流动相为0.1%甲酸水-0.1%甲酸乙腈,流速0.45 mL·min-1梯度洗脱,采用电喷雾(ESI) 离子源以正离子方式进行MRM检测,用时3 min。结果 阿普斯特在 2~600 ng·mL^-1 (r²=0.997 7)范围内线性关系良好,准确度和精密度均小于15%。空腹和餐后条件下阿普斯特片受试制剂AUC_0-t、AUC_0-∞和C_max的90% CI为参比制剂相应参数的80.00 %~125.00 %范围内。结论 受试制剂与参比制剂具有生物等效性。     

UPLC-MS/MS测定减肥食品中8种非法添加化学成分

目的 建立一种简便有效检测减肥食品中非法添加化学成分的UPLC-MS/MS检测方法。方法 采用UPLC-MS/MS法,以Eclipse Plus C₁₈（2.1 mm×50 mm,1.8 μm）色谱柱分离,串联四级杆质谱仪检测,多反应监测模式进行定性定量分析,以流动相A（0.02 mol·L^-1乙酸铵水溶液）-B（甲醇）进行梯度洗脱;柱温：40℃;流速：0.3 mL·min^-1,进样量2 μL。样品以甲醇为溶剂超声提取,快速定性定量检测非法添加在减肥食品中的麻黄碱、咖啡因、呋塞米、芬氟拉明、酚酞、N-单去甲基西布曲明、N,N-双去甲基西布曲明、西布曲明8种化学成分。结果 8种减肥类化学成分质谱检测的线性范围宽,相关性R² ≥ 0.995;方法检测限为0.042~0.175 μg·mL^-1,定量限为0.126~0.525 μg·mL^-1,方法精密度RSD（n=6）为1.7%~4.7%;3个浓度水平的平均回收率为90.3%~105.1%。结论 本方法专属性强、操作简单、方便快捷,可作为食品中非法添加减肥类化学成分的有效检测方法。     

UPLC同时测定中成药和保健食品中16种非法添加的抗过敏类药物

目的 建立UPLC测定中成药和保健食品中16种非法添加的抗过敏类药物。方法 采用Waters BEH C₁₈色谱柱（100 mm×2.1 mm,1.7 μm）,以甲醇-20 mmol·L^-1磷酸二氢钠（用磷酸调节pH值至3.0）为流动相,梯度洗脱,检测波长为220 nm。结果 16种抗过敏类药物在2.5~40 μg·mL^-1内呈良好线性关系（r²>0.999）,平均回收率为90.77%~113.35%,RSD为0.06%~1.21%;定量限为0.18~3.92 μg·mL^-1,检出限为0.09~0.78 μg·mL^-1。结论 该方法简便、灵敏度高,可有效地判断中成药及保健品中是否非法掺入16种抗过敏类药物。     

ＵＰＬＣ/ＭＳ/ＭＳ检测好康舒胶囊中非法添加降糖类化学药物

摘 要 目的：对好康舒胶囊进行添加降糖类化学药物进行检测。方法: 采用超高效液相色谱 串联质谱（UPLC-MS/MS）法,ACQUITY BEH C₁₈柱（50 mm×2.1 mm,1.7 μm）;以甲醇和0.01 mol·L^-1的乙酸铵溶液进行梯度洗脱。通过分子离子峰、二级质谱的碎片离子信息及多反应监测（MRM）模式下色谱峰的保留时间等信息,对本品中是否含盐酸二甲双胍等11种化学降糖药物的检出情况进行判定。 结果: 对11种化学降糖药物检测分析,好康舒胶囊中检出盐酸苯乙双胍及格列苯脲二种化学降糖药物。结论:好康舒胶囊中非法添加了盐酸苯乙双胍和格列苯脲化学降糖药物。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.