Determination of hydrophobicity of organic bases on poly(butadiene)-coated alumina and on octadecylsilica columns

Summary The performance of two chromatographic (HPLC) methods recommended for hydrophobicity evaluation of structurally diverse (noncongeneric) solutes was compared. Azole derivative drugs possessing properties of weak organic bases were used as the test solutes. One of the methods, recommended by Minick and co-workers, consists on suppressing specific interactions with the stationary phase (ODS) by adding modifiers to the eluent of neutral pH. The other method, developed previously in our laboratory, yields retention data for nonionized bases due to using poly(butadiene)-coated alumina (PBCA) columns which can be operated under alkaline conditions. It has been demonstrated that in the case of basic solutes, hydrophobicity parameters obtained by the method employing PBCA columns are more reliable. The noncontrolled specific interactions of organic bases with the ODS phase at pH 7.0 remain effective in spite of special precautions undertaken.     

Identification of chiral selectors for improved enantioseparation based on molecular interaction fields

Chiral sulfoxide drugs such as omeprazole, lansoprazole and pantoprazole were chromatographed on three chiral stationary phases (CSP), using amylose tris-(phenylcarbamate) derivatives in the reversed-phase mode. The retention factors (k) and chromatographic partition coefficients (k_w), obtained by extrapolation of the first according to the linear Snyder equation, were analyzed employing molecular interaction fields (MIF) of eluted analytes. Based on the generated MIF, chiral selectors could be identified for improving enantiomeric separation performance of the respective sulfoxides. The method is useful for predicting the complementarities between CSP and analytes, and thus to help the selection of appropriate stationary phases prior to their preparation.     

支链淀粉-三(苯基氨基甲酸酯)手性固定相的制备及酸性外消旋药物联苯双酯的拆分

合成并制备了支链淀粉－三（苯基氨基甲酸酯）手性固定相，利用高效液相色谱首次拆分了酸性外消旋药物联苯双酯，考察了流动相中异丙醇含量对拆分的影响。     

抗肿瘤药双萘酰亚胺的研究进展

DNA嵌入剂双萘酰亚胺是一种新型的抗肿瘤药物。从它的合成方法、结构与性质的关系以及与DNA的相互作用等方面综述了抗肿瘤药物双萘酰亚胺的研究进展。     

RETRACTED ARTICLE: Determination of sulpha drugs and ascorbic acid,individually or in mixture,withN-chlorosuccinimide

New spectrophotometric and titrimetric methods for the determination of sulphonamides withN-chlorosuccinimide (NCS) were developed. The spectrophotometric measurements can be made at 324–395 nm at pH 7.4 at room temperature, the stoichiometry being 1: 2, (p-H₂N-C₆H₄-SO₂NHR): (NCS) forming a dibromination product in presence of acidified potassium bromide. Potentiometrically or visually using methyl red as indicator, sulphonamides are titrated in pharmaceutical preparations by NCS always in presence of acidified potassium bromide. Ascorbic acid is determined alone and also in combinations, by first titrating it using potassium iodide and starch or 2,6-dichlorophenolindophenol as indicator. Acylation or diazotization of the aromatic amino groups that prevents substitution at the two ortho positions, is used as additional prereaction to analyze various binary and ternary mixtures of certain sulphonamides. These methods are accurate, simple, rapid, reproducible, useful at higher concentrations, do not involve any preseparation, and can tolerate several compounds that cause interference in other methods.Paper presented at the Eastern Analytical Symposium, New York, USA, 1985, No. 168     

21世纪中国新药研究开发策略探讨

分别从仿制药物、me-too药物及创新药物三方面入手,分析目前的现状及存在的问题,从知识产权、工作思路、制度规范、企业重组等角度探讨我国制药工业在加入WTO后应采取的新药研究开发策略。     

Enantioseparation of Some Clinically Used Drugs by Capillary Electrophoresis Using Sulfated β-Cyclodextrin as a Chiral Selector

The enantiomeric separation of 37 clinically used racemic basic drugs among 50 drugs was achieved using sulfated β-cyclodextrin (S-β-CD) as chiral selector at pH2.5 and in the reversed polarity mode. The results obtained in this study were different from the one obtained using neutral β-CD and its derivatives as chiral selectors. Using S-β-CD as chiral selector did not require the presence of the substructure 4H to achieve chiral separation as observed with β-Cyclodextrin (β-CD) and its derivatives since among the 37 separated drugs only 7 possess the 4H substructure. The chiral discrimination depends on the appropriate interaction between the analyte and the sulfated β-cyclodextrin.     

Fluorine in medicinal chemistry: Recent therapeutic applications of fluorinated small molecules

Advances in the development of newly developed fluorinated drugs, approved or in clinical trials, as organized by biological targets/disease states, are reviewed. In a few cases, compounds in early stages of development will be discussed, particularly where new promising targets are involved. Important topics such as anticancer and antiviral drugs were covered in the two previous reviews in this series. Included herein will be fluorinated drugs for treatment of diseases of the central nervous system, various cardiovascular diseases and obesity, antibacterial agents, and antifungal therapy.     

新型环糊精衍生物单6-O-苯基胺甲酰基-β-环糊精的合成及其在手性药物毛细管区带电泳拆分中的应用

合成了新型的环糊精衍生物单6-O-苯基胺甲酰基—β-环糊精，并对合成产物进行了表征。以新型环糊精衍生物为手性选择剂，考察了手性选择剂浓度、缓冲液PH值和浓度及有机溶质对8种手性药物对映体的毛细管电泳分离的影响。结果表明：手性选择剂浓度和缓冲液PH值是影响药物对映体分离的重要因素，有机溶质亦对分离有很大影响。单6-O-苯基胺甲酰基—β-环糊精能使所研究的8种手性药物中的5种达基线分离，3种达部分分离。而在同样条件下．β-环糊精仅能使上述药物中的菜心安达部分分离(及。＝0．67)，这说明我们合成的环糊精衍生物手性拆分能力要强于天然环糊精。我们还就单6-O-苯基胺甲酰基-β-环糊精对手性药物可能的拆分机理进行了探讨。     

Apparent molar volumes and adiabatic compressibilities of aqueous solutions of amphiphilic drugs

The apparent molar volumes and adiabatic compressibilities of aqueous solutions of the amphiphilic tricyclic drugs, chlorpromazine, promethazine, promazine and imipramine have been determined from measurements of density and ultrasound velocity. Positive deviations of the apparent molar volume from the Debye-Hückel limiting law in dilute solution indicate possible premicellar association. The changes of molar volume and compressibility accompanying aggregate formation were appreciably smaller than those of typical surfactants, suggesting a more tightly packed aggregate. The magnitude of the increase in molar compressibility on micellisation of imipramine decreased with temperature rise between 20 and 35°C. The results are discussed in terms of the structure and hydration of the drug aggregates.