色谱指纹图谱相似度方法的研究进展

色谱指纹图谱相似度是中药质量控制的重要方法之一,研究中药色谱指纹图谱的相似度计算方法对于中药质量控制很有意义。作者介绍了数量相似度、相似性相似度和差异性相似度3类相似度方法的研究现状,分析了3类相似度方法各自的特点与局限,对相似度方法的改进进行了总结,并对相似度方法存在的问题、改进趋势与应用作出了展望。     

In silico prediction of rhabdomyolysis of compounds by self-organizing map and support vector machine

Rhabdomyolysis is a potentially lethal syndrome resulting in leakage of myocyte intracellular contents into the plasma. Some drugs, such as lipid-lowering drugs and antihistamines, can cause rhabdomyolysis. In this work, a dataset containing 186 chemical compounds causing rhabdomyolysis and 117 drugs not causing rhabdomyolysis was collected. The dataset was split into a training set (containing 230 compounds) and a test set (containing 73 compounds). A Kohonen’s self-organizing map (SOM) and a support vector machine (SVM) were applied to develop classification models to differentiate compounds causing and not causing rhabdomyolysis. Using the SOM method, classification accuracies of 93.3% for the training set and 84.5% for the test set were achieved; using the SVM method, classification accuracies of 95.2% for the training set and 84.9% for the test set were achieved. In addition, the extended connectivity fingerprints (ECFP_4) for all the molecules were calculated and analyzed to find the important features of molecules relating to rhabdomyolysis.     

血塞通注射液指纹图谱研究

目的采用超高效液相色谱-紫外检测器-质谱(UPLC/UV/MS)法对血塞通注射液进行指纹图谱研究,并对其有效成分进行定性。方法采用Waters Acquity UPLCTM BEH C18柱(100 mm×2.1 mm,1.7μm),以乙腈-10 mmol/L醋酸铵溶液进行二元线性梯度洗脱,流速0.2 mL/min。离子化模式为ESI+。结果得到了分离度和重现性均较好的血塞通注射液超高效液相色谱-紫外检测器-质谱指纹图谱,标示了8个共有峰。结论超高效液相色谱-紫外检测器-质谱法可以用于血塞通注射液的快速鉴定及质量控制。     

Drug–drug interaction through molecular structure similarity analysis

Background

Drug–drug interactions (DDIs) are responsible for many serious adverse events; their detection is crucial for patient safety but is very challenging. Currently, the US Food and Drug Administration and pharmaceutical companies are showing great interest in the development of improved tools for identifying DDIs.

Methods

We present a new methodology applicable on a large scale that identifies novel DDIs based on molecular structural similarity to drugs involved in established DDIs. The underlying assumption is that if drug A and drug B interact to produce a specific biological effect, then drugs similar to drug A (or drug B) are likely to interact with drug B (or drug A) to produce the same effect. DrugBank was used as a resource for collecting 9454 established DDIs. The structural similarity of all pairs of drugs in DrugBank was computed to identify DDI candidates.

Results

The methodology was evaluated using as a gold standard the interactions retrieved from the initial DrugBank database. Results demonstrated an overall sensitivity of 0.68, specificity of 0.96, and precision of 0.26. Additionally, the methodology was also evaluated in an independent test using the Micromedex/Drugdex database.

Conclusion

The proposed methodology is simple, efficient, allows the investigation of large numbers of drugs, and helps highlight the etiology of DDI. A database of 58 403 predicted DDIs with structural evidence is provided as an open resource for investigators seeking to analyze DDIs.     

三圣汤及其固体汤剂的HPLC指纹图谱比较

目的:探索三圣汤固体汤剂与传统汤剂主要化学成分的差异,确定三圣汤固体汤剂能否代替传统汤剂。方法:对三圣汤水煎剂及其固体汤剂的HPLC图谱进行比较,探索二者化学成分的差异。结果:从三圣汤水煎剂及其固体汤剂中共检测出24个峰,二者指纹图谱的相关系数为0.966。结论:三圣汤水煎剂及其固体汤剂主要化学成分的峰面积存在一定差异,但组成基本相同,其共有组分的比例相近。     

苦参3种方法提取液HPLC指纹图谱比较

目的:比较苦参半仿生提取法(SBE法)、醇提法(AE法)、水提法(WE法)3种方法提取液的HPLC指纹图谱。方法:以≤1000Da提取物为最终产物,比较苦参3种方法提取液指纹图谱的共有峰、峰对应关系、共有峰重叠率、特征指纹峰总峰面积、相似度。结果:SBE法、AE法、WE法≤1000Da提取物特征峰数依次为17、14、14,总峰面积依次为7230.0、6733.4、2792.1。结论:3种提取方法制得的≤1000Da提取物的HPLC指纹图谱特征峰个数及总面积以SBE液为最大,进一步验证了苦参以SBE法提取为佳。     

双黄连胶囊双波长毛细管电泳指纹图谱研究

目的 建立双黄连胶囊( Shuanghuanglian Jiaonang,SHLJN)双波长高效毛细管电泳指纹图谱(DW CEFP).方法 用三角形和四面体优化法优化出以50 mmol·L-1硼砂(含20 mmol·L-1β-环湖精和5％乙腈,磷酸调pH 7.55)为背景电解质(BGE),采用未涂层石英毛细管(75 cm×75 μm,有效分离长度57 cm),以色谱指纹图分离量指数(RF)为目标函数优化试验条件,运行电压12 kV,检测波长203 nm和256 nm.用均值法整合双波长谱的宏定性宏定量信息,用一级系统指纹定量法评价SHLJN质量.结果 以连翘苷(FST)为参照物峰,在203 nm和256 nm下检测,分别确定16和11个共有指纹峰,建立了DW-CEFP.用均值法整合后进行评价出S9样品质量极好,S2、S3、S4和S6样品质量很好,S1、S7、S10和S11样品质量好,S5、S8和S12样品质量良好.结论 基于双波长谱的一级系统指纹定量法对SHLJN整体定性定量分析具有信息全面、准确可靠的特点,为其质量控制提供一种新参考.     

基于5组分测定和6波长高效液相色谱指纹谱的双标定量指纹法建立六味地黄丸对照指纹图谱动态技术标准研究

目的 建立双标定量指纹法精确恢复对照指纹图谱(RFP)理论和方法,实现动态指纹图谱标准的校正和复原.方法 用RP-HPLC法对LWDHW中5组分进行定量分析和建立其6波长定量指纹图谱研究.结果 利用HPLC-DAD在最大吸收波长处同时测定了没食子酸、5-羟甲基糠醛和丹皮酚含量,结合等吸收双波长消去法对色谱峰完全重叠的芍药苷和马钱苷进行同时定量测定,建立210、230、246、265、280和310 nm LWDHW-HPLC指纹谱,用均值法整合6波长HPLC定量指纹谱.以5组分测定和6波长指纹谱鉴定结果分别聚类分析比较不同厂家产品质量差异,结果以后者更为准确可靠,在此基础上建立LWDHW双标定量指纹法技术标准.结论 基于多指标定量分析和平行多波长高效液相色谱指纹谱的双标定量指纹法能够找到产生RFP的标准制剂和实现实时随行定量检测LWDHW指纹图谱.这一方法再现了中药指纹图谱标准,为中药指纹图谱工业化整体定量控制中药质量建立了可行技术方法,是中药指纹图谱评价方法发展历程中的一次技术飞跃.     

不同采收期水竹所制竹沥的HPLC指纹图谱研究

目的建立竹沥的HPLC指纹图谱研究方法。方法采用王uP—HPLC法,DikmaDiamonsiPMC18柱（250nunx4．6mm,5μm）,乙腈-0．1％磷酸水溶液梯度洗脱,检测波长为254nm,流速为1．0mL/min。对10个不同采收期水竹制备成的竹沥检测,并进行相似度计算。结果建立了具有29个共有峰的竹沥指纹图谱;不同采收期水竹制备成的竹沥质量存在指纹特征的差异。结论该方法准确、重复性好,为竹沥的质量控制提供了理论依据。     

Development of HPLC fingerprints for Mallotus species extracts and evaluation of the peaks responsible for their antioxidant activity

Some Mallotus species are used in traditional medicine in Vietnam. To use certain species in Western medicines or as food supplements, they should be identified and quality control should be more strict, for instance, to avoid the erroneous switching of species. In species with interesting activities, the compounds responsible for them should be identified. For these identifications, HPLC fingerprint methodology can be used.In this paper, HPLC fingerprints of different lengths were developed for a number of Mallotus species. Secondly, a multivariate regression model was constructed to model the antioxidant activity of the Mallotus samples from the HPLC fingerprints with the aim to indicate peaks possibly responsible for this activity. For this purpose, after data pretreatment, the calibration technique partial least squares (PLS) was applied.