评“McCall观察方法”——对一种色谱系统分配效果观察方法的商榷

本文通过理论分析和文献数据的分析,对McCall提出的色谱系统分配效果的观察方法提出了不同的看法,认为McCall方法中的所谓logK并不是常数。McCall的方法无论在理论上和实践上都是不妥的。     

麻醉镇痛剂和β-阻断剂类兴奋剂检测方法的研究(英文)

本文对兴奋剂的检测方法进行了研究。十九种麻醉镇痛剂、九种β-阻断剂,一种刺激剂和一个内标物等共三十种药物可用配备有氮磷检测器和配备有质量选择检测器的气相色谱仪分别进行初筛和确证分析。     

VKORC1-3673G>A、CYP2C9*3、CYP4F2 rs2108622和CYP2C19*2基因多态性对中国汉族房颤患者华法林维持剂量的影响

目的 探讨VKORC1-3673G>A、CYP2C9^*3、CYP4F2 rs2108622和CYP2C19^*2位点基因多态性对中国汉族房颤患者华法林维持剂量的影响。方法 收集107例服用华法林达维持剂量的汉族房颤患者的血样和临床相关资料,应用PCR-RFLP法检测VKORC1-3673G>A、CYP2C9^*3、CYP4F2 rs2108622和CYP2C19^*2基因型,采用独立样本t检验分析基因型与华法林维持剂量的相关性。多元线性回归建立给药模型,探讨基因多态性对华法林维持剂量的影响。结果 VKORC1-3673G>A、CYP2C9^*3、CYP4F2 rs2108622基因多态性和患者年龄、体质量能解释45.2%的华法林维持剂量差异。CYP2C19^*2基因多态性对本研究人群华法林维持剂量无影响。结论 VKORC1-3673G>A、CYP2C9^*3、CYP4F2 rs2108622基因多态性显著影响中国汉族房颤患者的华法林维持剂量。     

雌二醇11位含氧取代物的合成

为了进行抗辐射损伤药物的研究,参照文献从△⁹⁽¹¹⁾-雌二醇合成了11α-甲氧基雌二醇(12),对一些方法进行了改进。并从其中间体(3)合成了11α-羟基雌二醇(11)、11β-羟基雌二醇(13)、11β-甲氧基雌二醇(14)和11α-甲氧基-9β-雌二醇(15)。产物及关键中间体的核磁共振氢谱、质谱、元素分析等符合其结构。     

GSTP1、GSTM1基因多态性与顺铂导致骨髓抑制的相关性研究

目的考察顺铂致骨髓抑制与谷胱甘肽硫转移酶P1(GSTP1)和谷胱甘肽硫转移酶M1(GSTM1)基因多态性的关系。方法用病例对照研究的方法考察以顺铂为主要化疗方案的100例癌症初治肿瘤化疗患者基因多态性与骨髓移植的相关性,白细胞计数和血小板的数量为指标判断是否发生了骨髓抑制以及骨髓抑制程度。提取DNA扩增测序法判断GSTP1、GSTM1基因型。结果 GSTP1的3种基因型AA、AG、GG型均存在,并且在62例发生骨髓抑制的病例中,GSTP1 AG/GA型的患者的分布明显高于GSTP1 AA型患者。GSTM1包含缺失(-)和非缺失(+)2种基因型,100例病例中GSTM1(+)少于GSTM1(-)。Logistic分析结果表明GSTP1 AG/GG型是顺铂致骨髓抑制的独立危险因素,GSTM基因缺失虽不是顺铂致骨髓抑制的独立危险因素,但能促进GSTP1 AG/GG型的作用,导致顺铂致骨髓抑制进一步加重。结论顺铂导致的骨髓抑制程度与GSTP1基因多态性相关。     

亮叶杨桐的三萜皂苷类成分

为研究亮叶杨桐(Adinandra nitida Merr. ex Li)叶的化学成分，亮叶杨桐叶的乙醇提取物经大孔树脂、硅胶、Sephadex LH-20以及ODS柱色谱分离得到6个化合物，通过波谱(¹H NMR、 ¹³C NMR、 HR-ESI-MS)和化学方法进行结构鉴定，6个化合物分别被鉴定为2α,3α,19α-trihydroxy-olean-12-en-28-oic acid-28-O-β-D-glucopyranoside (1)、 arjunetin (2)、 sericoside (3)、 glucosyl tormentate (4)、 nigaichigoside F1 (5)和arjunglucoside I (6)。化合物1为新化合物，化合物2～6均为首次从该植物中分离得到。     

NUDT15c.415C>T和TPMT*3C基因多态性检测方法的比较与临床应用

目的 建立准确、快速、经济的方法,检测NUDT15 c.415C>T和TPMT*3C基因多态性,探讨临床应用价值。方法 收集2017年5月-2018年5月期间福建汉族患者服用硫唑嘌呤2周以上的血清样本,提取DNA或白细胞后分别采用PCR-RFLP法、PCR-Sanger测序法和荧光定量PCR法对NUDT15 c.415C>T和TPMT*3C进行基因多态性分型,比较这3种方法的准确性、简便性及经济性。根据白细胞值分组,结合临床资料,探讨基因多态性等因素与硫唑嘌呤致白细胞减少的相关性。结果 共纳入129例患者,其中硫唑嘌呤致白细胞减少15例（11.6%）。3种方法的基因多态性检测结果一致,TPMT*3C未发现突变纯合子。携带NUDT15c.415C>T突变等位基因者服用硫唑嘌呤致白细胞减少的风险高于携带野生等位基因者（OR=6.2,95%CI：2.5~15.4,P=0.000 054）,而携带TPMT*3C突变等位基因者与野生等位基因者出现白细胞减少比例并无显著性差异（P=0.393）。NUDT15c.415C>T基因多态性预测白细胞减少敏感度为53.3%,特异度为85.1%,ROC曲线AUC为0.69。结论 3种方法都可用于临床检测NUDT15 c.415C>T和TPMT*3C基因多态性。PCR-RFLP法不需要专用试剂盒,也不需要昂贵的仪器设备,成本较低,过程简单,易于操作,特别适合条件有限的单位开展工作。福建汉族患者在服用硫唑嘌呤前进行NUDT15c.415C>T基因多态性检测比TPMT*3C更具临床价值。     

牛膝甾酮25位差向异构体的分离与鉴定

目的分离并确定苋科植物怀牛膝(Achyranthes bidentata Blume.)中牛膝甾酮25位差向异构体的结构。方法利用色谱技术分离纯化牛膝甾酮25位差向异构体，用波谱(IR,UV,MS,NMR)方法及化学方法确定结构。结果从怀牛膝的乙酸乙酯部位分离得到3个化合物，分别鉴定为25S-牛膝甾酮(1, 25S-inokosterone)，25R-牛膝甾酮(2, 25R-inokosterone)，β-蜕皮甾酮(3, ecdysterone)。结论化合物1和2为首次从怀牛膝中分离得到的25位差向异构体，首次确定了25位绝对构型和发表该25位差向异构体的¹³CNMR数据。     

国产醋酸甲地孕酮的质量研究:6-羟基-6-甲基-17α-乙酰氧基黄体酮差向异构体的分离与鉴定

用柱层析及薄层层析对国产醋酸甲地孕酮的杂质进行了分析,共分离出7个杂质点:Ⅰ₁,Ⅰ₂,Ⅰ₃,Ⅰ₄,Ⅰ₅,Ⅰ₆,Ⅰ₇,并对其中Ⅰ₃和Ⅰ₄进行分离纯制及光谱分析,确定其结构为6β-羟基-6α-甲基-17α-乙酰氧基黄体酮及其差向异构体6α-羟基-6β-甲基-17α-乙酰氧基黄体酮。本文报道了薄层层析条件(硅胶GF₂₅₄,展开剂:醋酸乙酯-甲苯=7:3)以及光谱鉴别的依据。     

基于Oncomine数据库及生物信息学方法挖掘FAM20C在宫颈癌中的表达及作用机制

目的 通过深度挖掘Oncomine数据库中的基因信息,分析FAM20基因家族在宫颈癌中的表达及其作用机制。方法 通过Oncomine数据库查找有关于FAM20基因家族的研究信息,并对其在宫颈癌中的表达进行初步分析,根据分析结果,在Oncomine数据库中摘录所选取的FAM20家族成员在宫颈癌中的生存信息,使用GraphPad Prism软件进行生存分析,根据结果探讨其临床意义,发现FAM20基因家族中仅FAM20C基因对宫颈癌患者的生存率有意义,再使用TCGA数据库对FAM20C基因在宫颈癌中的表达及生存信息进行验证。用cBioPortal分析FAM20C基因相关蛋白功能及途径富集,通过String构建FAM20C基因的相关蛋白网络图,分析蛋白富集的生理过程。结果 在Oncomine数据库中共收集33项FAM20家族成员在肿瘤组织及正常组织中表达差异的研究。对不同成员进一步分析发现,FAM20B、FAM20C在宫颈癌中的表达存在差异（P<0.05）。对FAM20B及FAM20C基因在Oncomine数据库中的表达情况及生存数据做进一步分析,发现FAM20C高表达时患者生存率降低（P<0.05）,与TCGA数据库所验证的结果大体相同。通过Genecards数据库收集到FAM20C相关蛋白DMP1、AMELX、AMBN、MEPE、ENAM、FGF23、AMTN、SPP1、AHSG,主要富集于牙齿及骨组织的发育调控、柱状上皮细胞的分化调控以及细胞黏附过程。结论 FAM20C基因可通过影响肿瘤细胞的迁移和侵袭,对宫颈癌患者的生存产生影响。同时,靶向FAM20C基因可能是宫颈癌潜在的诊断和治疗方法。     

Electrochemical determination of partition coefficients of drugs.

An electrochemical method for the determination of partition coefficients of drugs that can exist as ions in aqueous solutions is presented. The method involves cyclic voltammetry at the polarizable interface between two immiscible electrolyte solutions. Because n-octanol is an unsuitable solvent for electrochemical purposes, 1,2-dichloroethane, which has electronic properties similar to those of n-octanol, was used in the measurements. The values obtained could be correlated with the values for n-octanol-water partition taken from the literature by an approach based on the linear solvation relationship: log P1 = a log P2 + b; in this relationship, a and b are constants and P1 and P2 correspond to the two different organic and aqueous phase partition equilibria. Furthermore, aqueous diffusion coefficients of drugs were determined from voltammograms.     

High performance liquid chromatographic capacity factor and partition coefficient relationship in a benzamide series

High performance liquid chromatography was used to establish the relationship between capacity factor (log k') and partition coefficient (log P octanol/water) in a benzamides series.The Chromatographie parameter was correlated to log P values experimentally determined by the shake-flask method and to log P calculated from Rekker's molecular fragments approach.In both cases, for the 10 molecules studied, capacity factor on partition coefficient fit very closely a regression line.The linear model was tested for another molecule in the same series. When comparing the computed values and the experimental ones, it can be concluded that HPLC is a good tool in predicting partition coefficient in this series.     

Calculating partition coefficient by atom-additive method

A new atom-additive method is presented for calculating octanol/water partition coefficient (log P) of organic compounds. The method, XLOGP v2.0, gives log P values by summing the contributions of component atoms and correction factors. Altogether 90 atom types are used to classify carbon, nitrogen, oxygen, sulfur, phosphorus and halogen atoms, and 10 correction factors are used for some special substructures. The contributions of each atom type and correction factor are derived by multivariate regression analysis of 1853 organic compounds with known experimental log P values. The correlation coefficient (r) for fitting the whole set is 0.973 and the standard deviation (s) is 0.349 log units. Comparison of various log P calculation procedures demonstrates that our method gives much better results than other atom-additive approaches and is at least comparable to fragmental approaches. Because of the simple methodology, the `missing fragment' problem does not occur in our method. This revised version was published online in August 2006 with corrections to the Cover Date.     

Lipophilic and electrostatic forces encoded in IAM-HPLC indexes of basic drugs: their role in membrane partition and their relationships with BBB passage data

The membrane phospholipid affinity data, log k(w)(IAM), for 14 basic drugs spanning a wide lipophilicity range were measured by HPLC on two different phospholipid stationary phases, i.e. IAM.PC.MG and IAM.PC.DD2. These data related weakly with log P(N) values, the n-octanol/water partition coefficients of the neutral forms; poorer relationships were found with log D(7.0) values, the n-octanol/water partition coefficients of the mixtures of neutral and ionized forms at pH 7.0. The lack of collinearity confirms that, differently from partition in n-octanol/water, partition in phospholipids encodes not only lipophilic/hydrophobic intermolecular recognition forces but also ionic bonds, due to electrostatic interactions between electrically charged species and phospholipids, according to the "pH-piston hypothesis". This component of interaction was parameterized by Δ log k(w)(IAM) values; they are the differences between the log k(w)(IAM) values experimentally measured and the values expected for neutral isolipophilic compounds. Δ log k(w)(IAM) values of the various analytes changed almost linearly from positive to negative values at increasing lipophilicity. This behavior is consistent with an interaction mechanism with membrane phospholipids including two intermolecular interaction forces: (i) lipophilic/hydrophobic interactions, which decrease on ionization proportionally to the lipophilicity of the neutral forms, and (ii) electrostatic interactions, which increase on ionization and are quite constant for all the analytes at a given ionization degree. Since BBB passage of the considered compounds is supposed to be based on passive mechanisms, we investigated the possible relationships between log BB values, i.e. the logarithms of the ratio between brain and blood concentrations, and three physico-chemical parameters, i.e. (i) log P(N) (lipophilic interaction of the neutral form), (ii) log k(w)(IAM) (global interaction with phospholipids), and (iii) Δ log k(w)(IAM) (electrostatic component of interaction with phospholipids). The results suggest that the electrostatic interactions encoded in log k(w)(IAM) values might act as trapping forces in a phospholipid barrier. Actually, we observed an inverse linear dependence of log BB on Δ log k(w)(IAM) values, but only for the compounds showing positive Δ log k(w)(IAM) values. We conclude that the driving force for BBB passage is the lipophilicity of the neutral forms, log P(N), and not the lipophilicity actually displayed at the experimental pH, log D(7.0). Indeed, the latter does not adequately take into account the role played by protonation in the analyte/membrane interactions because protonation, although hindering membrane passage, can either reduce or enhance partition in phospholipids, depending on analyte lipophilicity.     

Direct measurement of octanol-water partition coefficients by high-pressure liquid chromatography.

A technique is presented for the direct measurement of octanol-water partition coefficients by HPLC. The method involves running solutes in octanol-saturated water as the mobile phase against water-saturated octanol entrained on an inert support. Log P correlates linearly with log tc for a number of standards. The measurable range in log P (so far) is -0.3 to +3.7. A critical review of chromatographic methods in Hansch analysis is given.     

Substituent effects on partition coefficients of barbituric acids

Precise partition coefficients in 1-octanol-water at 25 degrees C were determined for three 2-thiobarbituric acids and 14 barbituric acids with a wider range of substituents. The experimental log P values (log Pexp) of barbituric acids were correlated with the carbon number and the branching effect of the C5 substituent(s) by linear regression analysis. The carbon number term makes a major contribution to the partition coefficients. The contribution of the polar effect of the C5 substituents was insignificant in contrast to a previous report. Hydrophobic constants (pi) were determined for allyl, phenyl, and chloro-substituents, and these empirical pi values gave much closer predicted calculated log P (log Pcalc) values when applied to the reported log Pexp values.     

高压液相层析法测定分配系数——Ⅰ.反相层析法测定肉桂酸及有关化合物的分配系数

本文报道了用反相层析法测定分配系数(P)的方法,并测定了具有辐射防护作用的肉桂酸及有关化合物的分配系数。实验测得的log P值同Hansch π加和法所得到的计算值相符,偏差低于10%。高压液相层析法测定分配系数具有快速、重现性好和操作简便等优点。     

Rapid determination of conditional partition constants in an FIA system.

This paper presents a simple and rapid method for the screening of substances for their conditional partition constants in the chloroform-water system. Samples are injected in either aqueous or organic solution into the corresponding phase. After equilibration in segmented flow the amount of sample remaining is measured photometrically. Performing the measurements at a series of phase volume ratios enables calculation of conditional partition constants knowing neither the amount injected nor the absorptivity of the substance under study. The time needed for a determination is about 15 min per substance, in many cases even shorter and the sample consumption is, in most cases, less than 1 mg. These characteristics make the method suitable for screening purposes. A series of compounds has been examined with this method, and acceptable results for the conditional partition constants were obtained in the range 0.2 less than D' less than 100 (-0.7 less than log D' less than 2.0).