培美曲塞二钠的合成路线图解

培美曲塞二钠（pemetrexed disodium，LY-231514，1），化学名为N-[4-[2-（2-氨基-4，7-二氢-4-氧代-1H-吡咯并[2，3-d]嘧啶-5-基）乙基]苯甲酰基]-L-谷氨酸二钠盐，是美国Eli Lilly公司研发的多靶向抗叶酸剂，2004年首次在美国上市，与顺铂（qv）联用治疗间皮瘤，商品名A1imta。本品可抑制多种叶酸依赖性酶进而发挥抗癌作用。     

他氟前列素

2012年2月10日,FDA批准由Merck公司开发的他氟前列素（tafluprost）滴眼液（商品名为Zioptan）在美国上市。该药用于降低开角型青光眼或眼高压患者升高的眼内压[1]。他氟前列素的中文化学名称：1-（5Z）-7-{（1R,2R,3R,5S）-2-[（1E）-3,3-二氟-4-苯氧基-1-丁烯基]-3,5-二羟基环戊基}-5-庚烯酸异丙酯;     

抗高血压药 坎地沙坦(Candesartan)

1商品名Atacand2化学名（±）－1H-苯并咪唑-7-羧酸-2-乙氧基-1-[[2’（1-H四氮-5-基）[1，1’-二苯]-4-基]－1－[环己氧基）羰基]氧基]乙酯3开发与上市厂商（日本）武田公司开发，于1997年12月首次在瑞典上市，1998年12月在美国，法国，西班牙，意大利等国上市。1999年4月在加拿大上市，1999年5月在澳大利亚上市。4药效分类AT；受体桔抗剂5药理本品在体内经肠道吸收，完全水解为去酯坎地沙坦的活性代谢物。本品选择性地与AT受体的亚型1（AT；）结合，为非肽类AT；受体桔抗剂，其结合能力比同类药物氯沙坦强SO倍，且结合牢固，解离缓…     

盐酸环苯扎林的合成

盐酸环苯扎林（cyclobenzaprine hydrochloride，1），化学名为5-（3-二甲胺基亚丙基）二苯并[a，d]环庚烯盐酸盐，是美国Merck公司研发的肌肉松驰剂，现已在多国上市，商品名Flexeril，临床用于缓解肌肉痉挛及伴随的骨骼肌剧烈疼痛。本品起效快，解痉作用好，不良反应小，是该类病痛的首选药物^[1-3].     

超高效液相色谱法测定奥卡西平活性代谢产物血药浓度

[摘要]目的:建立测定人血清中奥卡西平活性代谢产物10,11-二氢-10-羟基卡马西平血药浓度的超高效液相色谱法。方法:采集静脉血样本,高氯酸沉淀蛋白,离心取上清液进样,色谱柱为Waters ACQUITY UPLCBEH C18（2.1 mm×50 mm,1.7 μm）,流动相为0.05%甲酸水溶液﹕乙腈=75﹕25,检测波长254 nm,流速0.20 mL/min,柱温40 ℃。结果:10,11-二氢-10-羟基卡马西平在5~100 μg/mL浓度范围峰面积与内标峰面积比值对浓度比值的线性关系良好（r＝0.999 9）,回收率、精密度、稳定性、准确度均在限度要求范围内。结论:该方法操作简单、准确、灵敏,可用于临床监测奥卡西平活性代谢产物10,11-二氢-10-羟基卡马西平血药浓度监测。     

烯烃高收率制备手性邻二醇新方法

烯烃在催化剂锇酸盐交换的氯磷灰石（CAP—OSO4有制法）和手性配体双（二氢奎宁-9）-2，3-二氮杂萘-1，4-二醚[（DHQ）2PHAL]或双（二氢奎尼丁-9）-2，3-二氮杂萘-1，4-二醚[（DHQD）2PHAL]作用下高选择性制备相应的手性邻二醇。8例收率71％～96％，ee值90％～97％。催化剂回收方便，循环利用5次，收率和ee值稳定。     

西洛多辛合成路线图解

西洛多辛（silodosin，1），化学名为2，3-二氢-1-（3-羟丙基）-5-[（2R）-2-[2-[2-（2，2，2-三氟乙氧基）苯氧基]乙胺基]丙基]-1H-吲哚-7-甲酰胺，是由日本Kissei公司研发的α1A-肾上腺素受体拮抗剂，临床用于治疗良性前列腺增生。本品于2006年2月首次在日本批准上市，美国FDA于2008年2月接收了新药申请。本文对1的合成路线进行了归纳（图1）。     

HPLC—MS法测定大鼠血浆中白藜芦醇衍生物（E）-3，5，4′-三甲氧基二苯乙烯的浓度

目的：建立测定大鼠血浆中白藜芦醇衍生物（E）-3，5，4′-三甲氧基-1，2-二苯乙烯的液相色谱-质谱法（HPLC-MS）定量分析方法。方法：血浆样品0．1mL，经乙腈沉淀蛋白后，以ODS Hypersil C18（5μm，250mm×4．6mm）为固定相，甲醇-10mmol·L^-1醋酸铵（0．2％甲酸）（80：20，v／v）为流动相，流速为0．85mL·min^-1；采用HPLC—MS，选择离子监测（SIM）法检测（E）-3，5，4′-三甲氧基-1，2-二苯乙烯（[M＋H]^＋，m／z271．3），卡马西平（[内标，M＋H]^＋，m／z237．5），保留时间分别为8．9，4．0min。结果：（E）-3，5，4′-三甲氧基-1，2-二苯乙烯的线性范围为0．01～5．0μg·mL^-1,r〉0．999；日内、日间精密度RSD小于12．9％；相对回收率在94．8％～104．7％之间，最低检出限为0．005μg·mL^-1结论：经方法学确证和稳定性评价，该方法成功用于大鼠血浆中（E）-3，5，4′-三甲氧基-1，2-二苯乙烯的定量测定。     

西拉普利合成路线图解

西拉普利（cilazapril，1），化学名为（1S，9S）-9-[[（1S）-1-乙氧羰基-3-苯丙基]氨基]八氢-10-氧代-6H-哒嗪并[1，2-α][1，2]二氮杂革-1-羧酸，由瑞士罗氏制药公司研制开发，1990年在瑞士首次上市，临床主要用于治疗各种程度的原发性高血压和肾性高血压，是一种特定的长效血管紧张素转化酶抑制剂（ACEI）^[1]。1的结构中有3个手性中心，     

西他列汀合成路线图解

西他列汀（sitagliptin,1）,化学名为（2R）-4-氧代-4-[3-三氟甲基-5,6-二氢[1,2,4]三唑[4,3-a]吡嗪-7（8H）-基]-1-（2,4,5-三氟苯基）-丁-2-胺,是美国Merck公司研发的二肽基肽酶-Ⅳ（DPP-Ⅳ）抑制剂,2006年10月,其磷酸盐（商品名Januvia）作为首个DPP-Ⅳ抑制剂被美国FDA批准上市，临床用于治疗2型糖尿病。1有一个手性中心，其构型为R型，合成关键主要为杂环3-三氟甲基．[1，2，4]三唑[4，3．α]哌嗪（9）的制备和手性的引入。     

Third-generation antiepileptic drugs: mechanisms of action,pharmacokinetics and interactions

This review briefly summarizes the information on the molecular mechanisms of action, pharmacokinetic profiles and drug interactions of novel (third-generation) antiepileptic drugs, including brivaracetam, carabersat, carisbamate, DP-valproic acid, eslicarbazepine, fluorofelbamate, fosphenytoin, ganaxolone, lacosamide, losigamone, pregabalin, remacemide, retigabine, rufinamide, safinamide, seletracetam, soretolide, stiripentol, talampanel, and valrocemide. These novel antiepileptic drugs undergo intensive clinical investigations to assess their efficacy and usefulness in the treatment of patients with refractory epilepsy.     

消风止痒颗粒中毛蕊花糖苷、焦地黄苯乙醇苷B1、升麻素苷、升麻素、5-O-甲基维斯阿米醇苷、亥茅酚苷、苍术素醇、白术内酯Ⅱ和苍术素的HPLC法测定及其化学计量学综合评价

目的建立HPLC法同时测定消风止痒颗粒中毛蕊花糖苷、焦地黄苯乙醇苷B1、升麻素苷、升麻素、5-O-甲基维斯阿米醇苷、亥茅酚苷、苍术素醇、白术内酯Ⅱ和苍术素,并采用化学计量学方法对检测结果进行综合评价。方法采用Agilent Zorbax SB-C18色谱柱(250 mm×4.6 mm,5μm);以乙腈-0.2%磷酸溶液为流动相,梯度洗脱;检测波长:330 nm(0~14 min检测毛蕊花糖苷和焦地黄苯乙醇苷B1)、254 nm(14~31 min检测升麻素苷、升麻素、5-O-甲基维斯阿米醇苷和亥茅酚苷)、270 nm(31~55 min检测苍术素醇、白术内酯Ⅱ和苍术素);体积流量0.9 mL/min;柱温25℃;进样量10μL。采用SPSS26.0统计软件对消风止痒颗粒中9种成分进行聚类分析和主成分分析。结果毛蕊花糖苷、焦地黄苯乙醇苷B1、升麻素苷、升麻素、5-O-甲基维斯阿米醇苷、亥茅酚苷、苍术素醇、白术内酯Ⅱ和苍术素分别在2.53~63.25、1.09~27.25、8.17~204.25、2.38~59.50、4.07~101.75、1.74~43.50、0.66~16.50、1.47~36.75、2.86~71.50μg/m L线性关系良好;平均回收率分别为99.01%、98.17%、100.13%、97.63%、98.72%、97.22%、96.93%、99.24%、100.01%,RSD值分别为1.42%、1.26%、0.72%、1.55%、0.84%、1.06%、1.18%、0.67%、0.95%;11批样品聚类分析为3类,主成分1~3是影响消风止痒颗粒质量评价的主要因子。结论该方法操作简便、重复性好,可作为消风止痒颗粒中多指标成分质量评价模式。     

Pediatric Obesity: Pharmacokinetic Alterations and Effects on Antimicrobial Dosing

Limited data exist for appropriate drug dosing in obese children. This comprehensive review summarizes pharmacokinetic (PK) alterations that occur with age and obesity, and these effects on antimicrobial dosing. A thorough comparison of different measures of body weight and specific antimicrobial agents including cefazolin, cefepime, ceftazidime, daptomycin, doripenem, gentamicin, linezolid, meropenem, piperacillin‐tazobactam, tobramycin, vancomycin, and voriconazole is presented. PubMed (1966–July 2015) and Cochrane Library searches were performed using these key terms: children, pharmacokinetic, obesity, overweight, body mass index, ideal body weight, lean body weight, body composition, and specific antimicrobial drugs. PK studies in obese children and, if necessary, data from adult studies were summarized. Knowledge of PK alterations stemming from physiologic changes that occur with age from the neonate to adolescent, as well as those that result from increased body fat, become an essential first step toward optimizing drug dosing in obese children. Excessive amounts of adipose tissue contribute significantly to body size, total body water content, and organ size and function that may modify drug distribution and clearance. PK studies that evaluated antimicrobial dosing primarily used total (or actual) body weight (TBW) for loading doses and TBW or adjusted body weight for maintenance doses, depending on the drugs’ properties and dosing units. PK studies in obese children are imperative to elucidate drug distribution, clearance, and, consequently, the dose required for effective therapy in these children. Future studies should evaluate the effects of both age and obesity on drug dosing because the incidence of obesity is increasing in pediatric patients.     

国内对头孢克肟的临床研究与评价

头孢克肟是第1种第3代口服头孢菌素类抗生素,由日本藤泽制药株式会社于1987年研制成功并首先在日本上市应用于临床,1989年在美国上市。1999年已在80多个国家得到广泛的临床使用。头孢克肟的制剂剂型的研究已发展有胶囊剂、颗粒剂、混悬剂、片剂(普通片剂、咀嚼片、分散片)等。笔者综述了国产头孢克肟与日本产头孢克肟在胶囊剂、颗粒剂、混悬剂、片剂(普通片剂、咀嚼片、分散片)等的药动学比较,以及头孢克肟与头孢泊肟、头孢克洛、头孢呋辛、头孢美他酯、头孢噻肟、头孢地尼、头孢特仑、头孢妥仑匹酯等体外抗菌活性及临床药效学比较。     

高效液相色谱法同时测定麻仁丸中大黄素、大黄酚、大黄酸、大黄素甲醚、芦荟大黄素的含量

目的建立麻仁丸中大黄素、大黄酚、大黄酸、大黄素甲醚、芦荟大黄素的含量测定方法。方法采用奥泰ALLTIMA-C18色谱柱(4.6 mm×250 mm,5μm),以甲醇(A)-0.1%磷酸溶液(B)为流动相,梯度洗脱[0~9min,60%A;9~20 min,60%→80%A;20~45 min,80%A];流速:1.0 mL.min-1;柱温:30℃;检测波长254 nm。结果大黄素、大黄酸、大黄酚、大黄素甲醚、芦荟大黄素线性范围分别为在9.08~81.72、8.4~75.6、13.42~120.7、7.56~68.04、8.2~73.8μg.mL-1,与峰面积线性关系良好,平均回收率分别为99.1%、99.6%、99.4%、99.8%、99.2%,RSD分别为2.0%、1.8、3.2%、1.1%、1.5%。结论本方法可作为麻仁丸中大黄素、大黄酚、大黄酸、大黄素甲醚、芦荟大黄素含量测定的一种准确、灵敏、可行的方法。     

Neuroscience and Hormesis: Overview and General Findings

This article provides a summary of an assessment of the occurrence and impact of hormesis in the neurosciences, including the areas of neuroprotection, neurite outgrowth, and drugs for Alzheimer's disease, Parkinson's disease, anxiety, pain, seizures, stroke, as well as in the areas of behavioral pharmacology, addictive drugs, stress biology including the Yerkes–Dodson law, and p-glycoprotein efflux activity. The findings indicate that the hormetic dose response has a common, if not dominant, presence in each of these diverse areas of neuroscience and further strengthens the conclusion that hormesis is highly generalizable, being independent of biological model, endpoint, and chemical class.     

Inductively coupled plasma and clinical biology. Toxicological applications

The multi-elementary quantitation method using inductively coupled plasma mass spectrometry has been widely developed for use with biological fluids. Many elements can be quantified simultaneously in biological fluids, including: Li, Be, B, Al, Mn, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Rb, Sr, Mo, Pd, Cd, Sn, Sb, Te, Ba, W, Pt, Hg, Tl, Pb, Bi, U. The validation procedure is described by the French Society of Clinical Biology. Results for urine are corrected after creatinine determination.We report applications in clinical toxicology and forensic toxicology. Advances in inductively coupled plasma mass spectrometry in the field of clinical biology are particularly important for toxicological analysis. This powerful tool is helpful for better patient care and for the search for cause of death.     

A Quantitative Exploration of Attitudes Out of Line with the Prevailing Norms Toward Alcohol,Tobacco, and Cannabis Use Among European Students

The study examines groups of 15–16-year-old students whose attitudes toward drug use are out of line with the prevailing norms. It analyzes data from eight countries from the 2003 European School Survey on Alcohol and Other Drugs (ESPAD): Bulgaria, the Czech Republic, Hungary, France, Malta, Slovenia, Sweden, and the United Kingdom. In those countries, 22,900 15–16-year-old pupils answered the ESPAD questionnaire. Groups of subjects whose responses are far removed from the modal value are sought and studied. The aim is to explore “rare answers” compared to what is perceived by the majority of students. In order to explore what can lead a pupil to an atypical perception of risk, a cluster analysis, based on the risk perceptions of alcohol, tobacco, and cannabis use, was run to isolate the groups in which pupils tend to answer differently. Six clusters were established classifying students into those who failed to respond, deny the risks, do not know about the risks, see any drug use as great risk, see regular use as great risk, and who see a moderate risk for most frequencies of use. The nonresponders, risk deniers, and those ignorant of the risks are infrequent making up, in all, only 16.9% of the total sample. Gender, country, alcohol use, cannabis use, tobacco use, and friends’ consumption were used to describe both the individual risk perceptions and the clusters based on them. Both global context (country) and “micro” context (frequencies of drug use, peers lifestyle, and parental permissiveness) appear to play a major role in the risk perception of drug use.     

［~3H］二氢埃托啡在大鼠脑分布的定量放射自显影

本文用体外定量受体放射自显影分析法观察了［３Ｈ］二氢埃托啡（ＤＨＥ）在大鼠脑中定位分布和结合特点。结果表明，［３Ｈ］ＤＨＥ特异结合较高的部位主要为纹状体，伏隔核，大脑皮质Ⅰ层和Ⅲ层，丘脑，缰核，杏仁核。脚间核和蓝斑，ＤＨＥ主要作用于ｕ－阿片受体．