Analysis of creams

The possibilities for the determination of active components in creams by acid-base titrations in non-aqueous solvents were investigated. Interference by cream-base components with the titration of weak organic bases and their halides with perchloric acid in acetic acid, and with the titration of weak acids with tetrabutylammonium hydroxide in N,N-dimethylformamide were studied. It appeared to be possible to determine alkaloid halides, salicylic acid, hexachlorophene and methyl salicylate without previous clean-up of the cream samples.     

Theoretical problems associated with the use of acetic anhydride as a co-solvent for the non-aqueous titration of hydrohalides of organic bases and quaternary ammonium salts

A potentiometric titration study of organic base hydrohalides and quaternary ammonium salts using perchloric acid as the titrant and a mixture of acetic anhydride and acetic acid as the solvent was carried out and the titration mixture was analysed by NMR in order to clarify the chemistry of the reactions involved. It was found that in contrast to the general belief the formation of acetyl halides and titratable free acetate ion does not take place prior to the titration but NMR spectra proved the formation of acetyl halides in the course of the titration. This observation and the fact that the shape of the titration curves depends on the nature of the hydrohaloic acid bound to the base or of the anion in the quaternary ammonium salts led to the conclusion that the titrating agent is acetyl perchlorate formed in situ during the titration. Equations of the reactions involved in the titration process are shown in the paper.     

卡托普利的Gran图解测定法

以电位滴定为测定手段,用 Gran 图解法测定卡托普利的含量。该法以0.1mol/L KCl 溶液为离子强度调节剂,分步等体积滴入滴定剂,测定相应的 pH 值;按强碱滴定弱酸计量点后之 Gran 函数,对滴定剂体积作图,用直线外推法求滴定终点。     

甲磺酸地拉韦啶解离常数及分配系数的测定

目的:测定甲磺酸地拉韦啶的解离常数和分配系数。方法:采用酸碱滴定法测定不同体积比的甲醇-水溶液中的药物pKa值,再外推至纯水中药物浓度无限稀释时的pKa值。采用HPLC法测定药物的分配系数。结果:甲磺酸地拉韦啶的pKa为4.635,1gP值为2.907。结论:甲磺酸地拉韦啶为弱酸性亲脂性药物。     

月桂酰吲达帕胺的电离常数及分配系数的测定

目的测定月桂酰吲达帕胺的电离常数(pKa)及分配系数。方法采用酸碱滴定法测定各不同体积比的丙酮-水溶液中药物半中和点时的pH值作为药物在该体积比的丙酮-水溶液中的pKa值,再外推至纯水中药物浓度无限稀释时的pKa值;采用HPLC配合摇瓶法测定药物的分配系数。结果月桂酰吲达帕胺的pKa为3.87,lgP值为3.190。结论月桂酰吲达帕胺为弱酸性亲脂性药物。     

Potentiometric titration of thiols, cationic surfactants and halides using a solid-state silver-silver sulphide electrode

A rugged, low resistance silver-silver sulphide solid-state electrode for determining pharmaceuticals as authentic samples or in dosage forms by potentiometric titration is described. Sodium tetraphenylborate, mercury(II) acetate and silver nitrate (0.01) M were employed as titrants in the analysis of cationic surfactants (cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride and chlorhexidine salts), antithyroid drugs (methimazole and propylthiouracil) or sodium halides respectively.     

Sources of error in the European Pharmacopoeia assay of halide salts of organic bases by titration with alkali

A short overview has been given by the authors on the titrimetric assay methods of halide salts of organic bases in the pharmacopoeias of greatest importance. The alternative procedures introduced by the European Pharmacopoeia Commission some years ago to replace the non-aqueous titration with perchloric acid in the presence of mercuric acetate have also been presented and evaluated. The authors investigated the limits of applicability and the sources of systematic errors (bias) of the strongly preferred titration with sodium hydroxide in an alcoholic medium. To assess the bias due to the differences between the results calculated from the two inflexion points of the titration curves and the two real endpoints corresponding to the strong and weak acids, respectively, the mathematical analysis of the titration curve function was carried out. This bias, generally negligible when the pH change near the endpoint of the titration is more than 1 unit, is the function of the concentration, the apparent pK of the analyte and the ionic product of water (ethanol) in the alcohol-water mixtures. Using the validation data gained for the method with the titration of ephedrine hydrochloride the authors analysed the impact of carbon dioxide in the titration medium on the additive and proportional systematic errors of the method. The newly introduced standardisation procedure of the European Pharmacopoeia for the sodium hydroxide titrant to decrease the systematic errors caused by carbon dioxide has also been evaluated.     

益群生的非水溶液滴定法

作者对益群生含量测定试用了非水溶液滴定法。采用过氯酸冰醋酸溶液,以结晶紫为指示剂,滴定碱根部分;及甲醇钠在甲醇-苯混合液内,以麝香酚蓝为指示剂,滴定酸根部分,方法简便但以前法为优,试药配制较容易,且便于保存。     

氧化苦参碱的理化常数

目的测定氧化苦参碱的溶解度、解离常数(pKa)、油水分配系数(P)等理化常数,指导药物剂型的合理设计。方法按《中华人民共和国药典》中溶解度的测定方法测定氧化苦参碱在不同溶剂中的近似溶解度;采用电位滴定法、分光光度指示剂法测定氧化苦参碱的pKa值;采用摇瓶法测定氧化苦参碱在不同pH下的表观油水分配系数。结果氧化苦参碱在水、0.15 mol.L-1柠檬酸、0.15 mol.L-1碳酸钠溶液、甲醇、氯仿中溶解良好,在质量分数为20%的氢氧化钠溶液、石油醚和乙酸乙酯中溶解度都很低;电位滴定法、分光光度指示剂法测得的氧化苦参碱pKa分别为6.98、6.71;氧化苦参碱表观油水分配系数随着pH值的增加而增加,其真实油水分配系数为0.2。结论氧化苦参碱是一个亲水性很强的弱碱性药物。     

Acid dissociation and metal complex formation constants of penicillamine, cysteine, and antiarthritic gold complexes at simulated biological conditions.

Ionization constants for acid functions of D-penicillamine, L-cysteine, thiomalic acid, and thioglucose were measured by pH titration at 37 degrees and 0.15 M ionic strength. Chelate formation constants for these ligands with calcium(II), iron(III), and gold(I) were then determined under the same conditions chosen to approximate the in vivo situation. Only iron(III) formed both 1:1 and 1:2 chelates with D-penicillamine, L-cysteine, and thiomalate; calcium formed weak and gold strong 1:1 complexes with all ligands studied. Because of precipitate formation, the stability constants for the systems thioglucose-iron(III), D-penicillamine-gold(I), and L-cysteine-gold(I) had to be determined indirectly with thiomalic acid as the competing ligand. The in vivo fate of antiarthritic gold(I) compounds remained uncertain, but gold(I) chelates probably persist as such for extended periods.     

Differentiating nonaqueous titration of aspirin, acetaminophen, and salicylamide mixtures.

Mixtures containing aspirin, acetaminophen, and salicylamide were assayed potentiometrically by nonaqueous titration. The difference in pKa values for these weak acids was sufficient to permit successful differentiation. The titrant was tetrabutylammonium hydroxide, and the titration solvent was dimethylformamide. The procedure was applied to commercial dosage forms.     

电位滴定法标定高氯酸滴定液及其应用

目的:建立一种用电位滴定法标定高氯酸滴定液的分析方法,并将其结果运用于多种化学原料药的分析。方法:采用电位滴定对高氯酸滴定液(用DG113-SC电极)进行标定,再以相同方法测定盐酸多巴酚丁胺、硝酸硫胺和甘氨酸的含量。结果:用电位滴定法标定,线性关系好(r=0.9999),精确度更高,重复性更好,并且可以避免人为视觉误差。用电位滴定法标定与传统的酸碱指示剂法标定相比,两者之间存在一定差异。将其运用到化学原料药的分析,两种标定方法的结果对含量测定存在系统误差。结论:在药物分析过程中,对于使用电位滴定法测定药品含量的滴定液,应使用电位滴定法来标定其浓度,可以减小方法误差,使测量结果更严密。     

炮制对山茱萸有效成分的影响研究

目的测定和分析山茱萸及其不同炮制品中马钱苷、莫诺苷、5-羟甲基糠醛、没食子酸、多糖、总黄酮、水溶性皂苷和有机酸的含量,评价炮制对山茱萸效应物质的影响。方法采用高效液相色谱法测定山茱萸不同饮片中马钱苷、莫诺苷、5-羟甲基糠醛和没食子酸的含量,采用比色法测定山茱萸不同饮片中多糖、总黄酮和水溶性皂苷的含量,采用酸碱滴定法测定山茱萸不同饮片中有机酸的含量。结果山茱萸经炮制后所测成分的含量都有不同程度的变化,除莫诺苷外,高压蒸制品所测成分的含量均略高于常压蒸制品,但均无显著性差异。结论高压蒸制工艺优于常压蒸制工艺,测定结果可为制定山茱萸最佳炮制工艺提供科学的依据。     

Kibdelins (AAD-609), novel glycopeptide antibiotics. II. Isolation, purification and structure

A new glycopeptide antibiotic complex was isolated from the fermentation culture of Kibdelosporangium aridum subsp. largum (SK&F AAD-609) by affinity chromatography on a D-alanyl-D-alanine agarose column. This major components of the complex were resolved by preparative reversed-phase HPLC. Mild acid hydrolysis showed that the new antibiotics have the same mannosyl aglycon (2) as the aridicins. FAB mass spectrometry, isoelectric focusing, potentiometric titration and carbohydrate and fatty acid analyses were used to determine the structures of the five major components of the complex. These studies showed that the kibdelins differ from the aridicins only in the oxidation level at the C-6 position of the amino sugar. Kibdelin A (5), B (6), C1 (7), C2 (8) and D (9) are a series of N-acylglucosamine analogs containing saturated straight and branched chain C10-C12 fatty acids whereas, in kibdelin D the fatty acid component is (Z)-4-decenoic acid.     

Isoelectric points of some sulfonamides: determination by microelectrophoresis and by calculations involving acid-base strength

The isoelectric points of four very slightly soluble sulfonamides were measured by microelectrophoresis of dilute suspensions as a function of pH. Ionic strength and pH were adjusted with KCl, KOH, and HCl only. The isoelectric points were also calculated from published values of acid and basic ionization constants which had been determined by potentiometric titration, and from changes in ultraviolet absorption spectra and in solubility as a function of pH. Including one sulfonamide whose isoelectric point as measured by microelectrophoresis was published, rather good agreement between the two methods was observed for all but one compound. All values were between 3.5 and 4.6, indicating that the sulfonamides function as weak acids rather than as amphoteric compounds at physiological pH.     

酸碱滴定过程的计算机模拟

酸碱滴定法是一种常用的容量分析方法,但在实验室条件下计算酸碱混合体系的pH值和绘制滴定曲线非常繁琐。本文依据酸碱滴定理论,推导出滴定百分数φ与H~+浓度的数学表达式,利用Visual Basic 6.0语言通过计算机编程,实现了酸碱滴定过程精确pH值的计算和滴定曲线的绘制,并能动态模拟滴定过程。     

市售中药炮制用辅料醋的质量考察

目的:对市售中药炮制用辅料醋的质量进行考察。方法:采用薄层色谱(TLC)、高效液相色谱(HPLC)、滴定等方法,对市售食醋主要物质进行测定。结果:15批样品醋与对照品在TLC图相应位置上均检出相同颜色的斑点;15批样品醋可溶性无盐固形物的质量浓度为16.4⁷0.70 mg/ml;总酸质量浓度为38.070.70 mg/ml;总酸质量浓度为38.0⁵9.2 mg/ml,乳酸质量浓度为1.1659.2 mg/ml,乳酸质量浓度为1.16⁹.71 mg/ml。结论:市售醋质量差异较大,亟需建立较为全面的食醋质量标准。     

非水滴定与电位滴定法测定福尔可定含量的比较

目的对非水滴定和非水电位滴定法测定福尔可定的含量进行比较。方法均以冰醋酸为溶剂,非水滴定法采用结晶紫作为指示剂指示滴定终点,电位滴定法测定以第二个滴定突跃为滴定终点,两法均对滴定结果进行空白校正。结果电位滴定法滴定突跃明显,测定出的3批实际样品含量高于非水滴定的结果。结论因非水电位滴定法操作简单、滴定突跃明显,相较于非水滴定法能更好地控制福尔可定的质量。     

双嘧达莫2种定量分析方法的比较

目的:探讨高氯酸非水滴定法和高效液相色谱(HPLC)法测定双嘧达莫原料药含量的可行性。方法:非水滴定法采用电位法指示终点,并考察不同溶剂对滴定的影响;HPLC法中,色谱柱为C18,流动相为乙腈-20mmol·L-1磷酸二氢钾(含1.0%三乙胺,磷酸调pH至4.0)=35∶65;并与《中国药典》规定的溴酸钾滴定法进行比较。结果:非水滴定法、HPLC法和溴酸钾滴定法的含量分别为101.36%、101.11%、100.56%。结论:高氯酸非水滴定法和HPLC法均可用于双嘧达莫原料药的含量测定,且高氯酸非水滴定法操作更简便、快捷。     

Determination of free acid and anhydride content in aliphatic and aromatic cyclic anhydrides by conductometric titration

The simultaneous determination of free acid and anhydride content in samples of cyclic aliphatic and aromatic anhydrides was studied. Conductometric titration with methanolic sodium methoxide while using acetone as a solvent proves to be a reliable method, applicable to small amounts of sample (0.3 mmol). The results of the conductometric method were checked by potentiometric titration of free acid with trinonylamine, and by determination of the total acid content after complete hydrolysis of the sample.In honour of Professorpolderman on the occasion of his retirement.