硝酸甘油片有关物质的研究

目的：利用液相色谱法、化学反应法、紫外光谱法及离子色谱法对硝酸甘油片中显著色谱峰进行分析,并确定该目标峰的组分及检测方法,帮助生产企业解决硝酸甘油片质量标准中有关物质杂质峰的判定和扣除问题。方法：结合《中国药典》2015年版硝酸甘油片有关物质检查法与JP17版硝酸甘油片硝酸根离子限量检查法,对未知色谱峰定性,并通过离子色谱法进行定性及定量分析。结果：样品色谱图中2.4min处色谱峰为硝酸根离子与辅料的重叠峰,且以硝酸根离子为主。结论：本研究采用多种方法验证了未知色谱峰的主要成分为硝酸根离子,为《中国药典》2015年版中硝酸甘油片质量标准的修订提供了参考。     

双嘧达莫片中有关物质测定法方法的研究

目的：建立双嘧达莫片中有关物质的方法。方法：采用高效液相色谱法,色谱柱为Agilent XDB-C₁₈(4.6mm×250mm,5μm),流动相为0.1%磷酸氢二钠溶液(用磷酸调节pH值至4.6)-甲醇(25:75),检测波长为288nm,流速1.0mL.min^_-1。结果:双嘧达莫与其降解产物在该色谱条件下能够有效分离。结论:所建方法简便,专属性强,可以用于双嘧达莫片中有关物质的测定。     

HPLC测定异维A酸有关物质

目的 建立HPLC测定异维A酸有关物质的方法。方法 色谱柱为NUCLEOSIL 100-3 C₁₈（4.6 mm×150 mm,3 μm）,以甲醇-水-冰醋酸（770：225：5）为流动相,流速为1.0 mL·min^-1;柱温为25℃,检测波长为355 nm。结果 异维A酸峰与杂质H、I、维A酸、强制降解杂质峰分离良好;异维A酸、杂质H、I和维A酸的线性范围分别为0.000 545 5~21.82 μg·mL^-1（r=0.999 9）,0.002 856~7.14 μg·mL^-1（r=0.999 0）,0.002 789~6.97 μg·mL^-1（r=0.999 1）、0.017 07~22.76 μg·mL^-1（r=0.999 6）;检测限分别为0.27,0.60,0.65,5.50 ng·mL^-1,定量限分别为0.55,2.85,2.80,17.00 ng·mL^-1;杂质H、I和维A酸的平均回收率分别为101.57%,102.02%,101.03%,RSD分别为0.5%,0.8%,1.5%。结论 建立的HPLC方法准确、专属性强,可用于异维A酸有关物质的测定。     

Synthetic cathinones: an evolving class of new psychoactive substances

Abstract

Synthetic cathinones (SCat) are amphetamine-like psychostimulants that emerged onto drug markets as “legal” alternatives to illicit drugs such as ecstasy, cocaine, and amphetamines. Usually they are sold as “bath salts,” “plant food,” or “research chemicals,” and rapidly gained popularity amongst drugs users due to their potency, low cost, and availability. In addition, internet drug sales have been replacing the old way of supplying drugs of abuse, contributing to their rapid spread. Despite the legislative efforts to control SCat, new derivatives continue to emerge on the recreational drugs market and their abuse still represents a serious public health issue. To date, about 150 SCat have been identified on the clandestine drugs market, which are one of the largest groups of new psychoactive substances (NPS) monitored by the United Nations Office on Drugs and Crime and the European Monitoring Center for Drugs and Drug Addiction. Similar to the classical stimulants, SCat affect the levels of catecholamines in the central nervous system, which results in their psychological, behavioral and toxic effects. Generally, the effects of SCat greatly differ from drug to drug and relatively little information is available about their pharmacology. The present work provides a review on the development of SCat as substances of abuse, current patterns of abuse and their legal status, chemical classification, known mechanisms of action, and their toxicological effects.     

基于三种原理分离技术的多肽类药物比伐芦定杂质分析

摘要：目的 建立不同分离原理的高效液相色谱法,对7家企业的比伐芦定原料药中相关杂质进行分析,为全面控制比伐芦定有关物质提供依据。方法 采用反相高效液相色谱法（RP-HPLC）对11个杂质进行分离分析;采用亲水色谱法（HILIC-HPLC）对4个工艺杂质进行控制;采用分子排阻色谱法（SEC-HPLC）对聚合物进行测定。结果 建立的RP-HPLC方法可将主成分及11个杂质有效分离,11个杂质的校正因子均在0.8～1.2之间,比伐芦定检出浓度为0.1μg·ml-1,检测限为0.004%;建立的HILIC-HPLC方法可对主成分及4个工艺杂质有效分离,比伐芦定检出浓度为0.3μg·mL-1,检测限为0.01%;在SEC-HPLC条件下聚合物和比伐芦定依次出峰,两者分离度为2.9,比伐芦定检出浓度为6ng·mL-1,检测限为0.0006%。采用主成分自身对照法计算7家企业15批样品中15种已知杂质及聚合物,不同企业的产品杂质含量与其生产工艺存在一定的相关性。结论 三种不同原理的方法均专属性良好,灵敏度高,耐用性好,结果可靠,可用于比伐芦定有关物质的质量控制。     

一次性使用树脂吸附柱治疗尿毒症的临床观察

目的探讨1次性使用树脂吸附柱治疗尿毒症患者的疗效与安全性。方法维持性血液透析患者31例,采用血液灌流与血液透析(HP/HD)联合治疗方法与常规血液透析(HD)方法对比(自身对照)。治疗前后检测中分子物质(MMS)、血尿素、肌酐、白蛋白、血细胞及临床症状。结果树脂吸附柱治疗血液透析患者能显著清除尿毒症患者体内的中分子物质,单次使用治疗2hMMS平均下降25.0%,最高达44.4%。而普通透析对MMS无多大影响,两者差异具有显著性(P<0.001)。同时患者的睡眠、食欲、皮肤瘙痒有不同程度的改善。未发生其他任何不良事件和副作用。结论作为MMS的清除治疗措施,1次性使用树脂吸附柱临床使用安全、疗效可靠,无毒副反应。     

External quality assessment of human biomonitoring in the range of environmental exposure levels

The number of human biomonitoring (HBM) applications for identifying and assessing the chemical exposure of the general population from the environment has distinctly increased during the last decade. An appropriate external quality assessment of the applied methods is essential to assure the accuracy and the comparability of HBM results. The international programme of the German External Quality Assessment Scheme (G-EQUAS) provides proficiency testing for most of the HBM parameters, which are commonly used for the assessment of the human exposure to chemicals. Since 1992, G-EQUAS provides intercomparison runs for biological monitoring parameters in the environmental exposure range twice a year, with a successive increase of parameter numbers. In round no. 45 (2010) 18 metals in blood, plasma and urine und 36 organic parameters in urine and plasma were provided. Additionally analyses of 4 haemoglobin adducts were offered. For each parameter, two samples with different concentrations of the biomarker were sent to the participants. The target values as well as the tolerance ranges were estimated on the basis of the results from reference laboratories. The successful participation was certified, if the participant's results were within the tolerance ranges for both samples. The number of participants ranged from 3 to 37 international laboratories according to the individual parameter. The highest interest was observed for the detection of metals in blood, serum and urine, whereas only a few of the participants took part in the analyses of organophosphate metabolites and haemoglobin adducts. The rate of a successful participation ranged from 38 to 100%. Poor success rates were found for organophosphate metabolites, 1-naphthol and cotinine in urine. A training effect was observed for a group of laboratories which participated regularly in the analysis of organochlorinated compounds in serum.     

高血压病左心室肥厚与血管活性物质的关系及依那普利干预

目的：探讨体循环血液中多种血管活性物质在高血压病左心室肥厚（ＬＶＨ）发生和依那普利（ｅｎａｌａｐｒｉｌ）逆转治疗中的作用。方法：测定高血压病患者４５例合并ＬＶＨ、４５例不合并ＬＶＨ及３０例正常人血流动力学和血浆５种血管活性物质，观察２７例高血压病患者合并ＬＶＨ依那普利治疗２４周后各项参数变化。结果：合并ＬＶＨ组收缩压、血浆内皮素、去甲肾上腺素、内源性洋地黄物质（ＥＤＬＳ）和心钠素高于不合并ＬＶＨ组（Ｐ＜０．０５～０．０１），血管紧张素Ⅱ高于正常人（Ｐ＜０．０１）；对１３个相关因素进行逐步回归分析表明，内皮素、血管紧张素Ⅱ和去甲肾上腺素对ＬＶＨ作用显著（复相关系数０．７６９，Ｐ＜０．００１）；内皮素、血管紧张素Ⅱ、去甲肾上腺素、ＥＤＬＳ之间呈正相关（Ｐ＜０．０５～０．０１）；依那普利干预后，ＬＶＨ消退，血压和血管活性物质同步下降（Ｐ＜０．０５～０．０１）。结论：体循环血液中多种血管活性物质含量改变及其相互作用可能共同参与高血压病ＬＶＨ的形成，依那普利消退ＬＶＨ的机制可能与降低这些物质有关。     

Pharmacological study of a new hypoglycaemic sulphonamide: Glisoxepid (RP 22410)

Summary Glisoxepid or RP 22410 is a new very active hypoglycaemic sulphonylurea. In the normal conscious dog, RP 22410 administered intravenously was 81 or 131 times more active than tolbutamide, depending on whether the dose is expressed in grams or in moles. The hypoglycaemic effect did not occur in the totally pancreatectomized dog. — RP 22410 stimulated insulin secretion.In vivo in the anaesthetized or conscious dog, the action of the drug (whether it be administered intravenously or orally) resulted in a rapid and considerable increase of the amount of insulin secreted by the pancreas. This action lasted several hours.In vitro the direct action of the product on the pancreas was demonstrated on the isolated and perfused rat pancreas, even at very low concentrations. — In the mouse, prolonged oral administration of RP 22410 stimulated neogenesis of the islets of Langerhans and of the beta cells. It therefore possesses betacytotrophic action.

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Pharmakologische Studie über das neue blutzuckersenkende Sulfonamid Glisoxepid RP 22410

Zusammenfassung Glisoxepid oder RP 22410 ist ein neuer, stark aktiver, blutzuckersenkender Sulfonylharnstoff. Je nachdem ob die Dosen in Gewichten oder Mol ausgedrückt werden, ist er am wachen Hund bei intravenöser Applikation 81 bzw. 131mal aktiver als Tolbutamid. Die blutzuckersenkende Wirkung zeigt sich nicht am vollständig pankreatektomierten Hund. -Diese Substanz stimuliert die Insulinsekretion.In vivo zeigt sich ihre Wirkung am anästhesierten oder wachen Hund in einer schnellen und beträchtlichen Erhöhung der vom Pankreas sezernierten Insulinmenge unabhängig davon ob sie intravenös oderper os verabreicht wird. Diese Wirkung bleibt über mehrere Stunden bestehen.In vitro wurde die direkte Wirkung der Substanz auf den isolierten und perfundierten Pankreas der Ratte auch in sehr geringen Konzentrationen nachgewiesen. -Bei der Maus stimuliert RP 22410 bei chronischer Verabreichungper os die Neubildung von Langerhansschen Inseln und B-Zellen. Sie besitzt daher eine betacytotrophe Wirkung.

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Etude pharmacologique d'un nouveau sulfamide hypoglycémiant: le glisoxepid (RP 22410)

Résumé Le glisoxepid ou RP 22410 est un nouveau sulfonylurée hypoglycémiant très actif. Chez le chien normal éveillé, administré par voie intraveineuse, il est 81 ou 131 fois plus actif que le tolbutamide, suivant que les doses sont exprimées en poids ou en moles. Cette action hypoglycémiante ne se manifeste pas chez le chien totalement dépancréaté. — Ce produit stimule la sécrétion d'insuline.In vivo chez le chien anesthésié ou éveillé, l'action du produit (que celui-ci soit administré par voie intraveineuse ou par voie digestive) se traduit par une augmentation rapide et considérable de la quantité d'insuline sécrétée par le pancréas. Cette action se prolonge pendant plusieurs heures.In vitro l'action directe du produit sur le pancréas a été démontrée sur le pancréas isolé et perfusé du rat, même à très faibles concentrations. — Chez la souris le RP 22410 administré chroniquementper os stimule la néogénèse des îlots de Langerhans et des cellules bêta. Il est donc doué de l'action bêtacytotrophe.

     

Internet Search and Krokodil in the Russian Federation: An Infoveillance Study

Background

Krokodil is an informal term for a cheap injectable illicit drug domestically prepared from codeine-containing medication (CCM). The method of krokodil preparation may produce desomorphine as well as toxic reactants that cause extensive tissue necrosis. The first confirmed report of krokodil use in Russia took place in 2004. In 2012, reports of krokodil-related injection injuries began to appear beyond Russia in Western Europe and the United States.

Objective

This exploratory study had two main objectives: (1) to determine if Internet search patterns could detect regularities in behavioral responses to Russian CCM policy at the population level, and (2) to determine if complementary data sources could explain the regularities we observed.

Methods

First, we obtained krokodil-related search pattern data for each Russia subregion (oblast) between 2011 and 2012. Second, we analyzed several complementary data sources included krokodil-related court cases, and related search terms on both Google and Yandex to evaluate the characteristics of terms accompanying krokodil-related search queries.

Results

In the 6 months preceding CCM sales restrictions, 21 of Russia''s 83 oblasts had search rates higher than the national average (mean) of 16.67 searches per 100,000 population for terms associated with krokodil. In the 6 months following restrictions, mean national searches dropped to 9.65 per 100,000. Further, the number of oblasts recording a higher than average search rate dropped from 30 to 16. Second, we found krokodil-related court appearances were moderately positively correlated (Spearman correlation=.506, P≤.001) with behaviors consistent with an interest in the production and use of krokodil across Russia. Finally, Google Trends and Google and Yandex related terms suggested consistent public interest in the production and use of krokodil as well as for CCM as analgesic medication during the date range covered by this study.

Conclusions

Illicit drug use data are generally regarded as difficult to obtain through traditional survey methods. Our analysis suggests it is plausible that Yandex search behavior served as a proxy for patterns of krokodil production and use during the date range we investigated. More generally, this study demonstrates the application of novel methods recently used by policy makers to both monitor illicit drug use and influence drug policy decision making.