Development of Electrophoretic Methods for Simultaneous Determination of Enantiomeric Ratio and Composition of Diastereomeric Salt Mixtures

Obtaining enantiomeric pure compounds is—among other techniques—possible in a resolvation experiment via diastereomeric salt formation, excellently exemplified by a modified Pope–Peachy method performed in supercritical carbon dioxide as solvent. The salt precipitation is followed by supercritical fluid extraction (SFE) to separate the diastereomeric salts and the unreacted enantiomers. To evaluate the extraction efficiency, conversion and enantioselectivity achieved, it is essential to determine the enantiomer excess and the residual resolving agent content in extracts and raffinates. Carefully chosen experimental parameters enable the simultaneous determination of certain anions and cations in capillary electrophoresis in a single run, which has not been reported for diastereomeric mixtures so far. In this paper, a partially validated chiral selective cyclodextrin enabled capillary electrophoresis method is presented for the characterization of cis-permethrinic acid samples resolved with (R)-1-phenylethylamine prepared by the SFE-based resolvation technique. To evaluate the efficiency of the resolvation, a cyclodextrin enabled chiral separation method was developed applying permethylated-β-cyclodextrin as chiral selector. The theoretical possibility of the widespread application of the developed method (with minor adjustments) is justified for other selectands and selectors. The developed methods can be thereby applied for the fast and reliable control of resolvation experiments.     

Non-Racemic Mixtures of 1,3,2-Oxazaphosphacyclanes - Enantiomeric Composition Determination by NMR

Abstract

The enantiomeric ratio in non-racemic mixtures of 2-anilino-2-oxo-1,3,2-oxazaphospho-rinane (I) and 3-(α-rnethylbenzyl)-(I)¹ enantiomers was determined by measurement of the integral intensity ratio of two ³¹P-NMR signals, assigned to enantiomers and differentiated due to the effect of statistically controlled associate-diastereoisomerim (scada), ² when association occurs under conditions of fast exchange.     

Development and Validation of LC Method for Simultaneous Determination of Two Binary Mixtures Containing Indapamide

A new sensitive, simple, rapid, and precise RP LC method with hydrochlorothiazide as internal standard has been developed for resolving two binary mixtures, perindopril with indapamide and captopril with indapamide, in pharmaceutical formulations. The drugs were separated at room temperature on a 250 mm × 4.6 mm, 5-μm particle, cyanopropyl column with 10 mm KH₂PO₄, pH 6.0-methanol 55:45 (v/v) as mobile phase at a flow rate of 1 mL min^?1. Detection was at 210 nm. Factors affecting the separation process were studied and optimized. The linearity, accuracy, and precision of the method were good, and the method was successfully applied to the determination of the two binary combinations in synthetic mixtures and commercial pharmaceutical products.     

Simultaneous Determination of Concentration and Enantiomeric Composition of Amino Acids in Aqueous Solution by Using a Tetrabromobinaphthyl Dialdehyde Probe

3,3′-Diformyl-1,1′-bi-2-naphthol or its methoxymethyl-protected derivative is found to undergo a highly selective reaction with excess bromine in CH₂Cl₂ at reflux to give the novel 5,5′,6,6′-tetrabrominated product (S)- or (R)- 2 . The observed electrophilic substitution at the 5,5′-positons of an optically active binaphthyl compound is unprecedented. Unlike unbrominated 3,3′-diformyl-1,1′-bi-2-naphthol, which is not suitable for fluorescent recognition in water, compound (S)- 2 , in combination with Zn²⁺, exhibits a highly enantioselective fluorescent response toward amino acids in aqueous solution (HEPES buffer, pH 7.4). It is further found that the condensation product of (R)- 2 with tryptophan, (R)- 3 , shows dual-responsive emissions toward amino acids; the short wavelength (λ₁=350 nm) emission is sensitive to the concentration of the substrate regardless of the chiral configuration and the long wavelength (λ₂>500 nm) emission is highly enantioselective. Thus, the use of (R)- 3 allows the simultaneous determination of the concentration and enantiomeric composition of an amino acid sample from one fluorescence measurement.     

Phosphorus Containing Achiral Reagents for the Determination of Enantiomeric Composition of Chiral Alcohols

Abstract

It is shown that P₄S₁₀ and (R₂N)3P can be used as achiral derivatising reagents for the determination of enantiomeric excess (ee) of chiral alcohols R*OH.     

Development of Validated Chromatographic Methods for the Simultaneous Determination of Metronidazole and Spiramycin in Tablets

Two chromatographic methods have been described for the simultaneous determination of metronidazole (MET) and spiramycin (SPY) in their mixtures. The first method was based on a high performance thin layer chromatographic (HPTLC) separation of the two drugs followed by densitometric measurements of their spots at 240 nm. The separation was carried out on Merck TLC aluminum sheets of silica gel 60 F₂₅₄ using methanol: chloroform (9:1, v/v) as a mobile phase. Analysis data was used for the linear regression line in the range of 1.0–2.0 and 0.8–2.0 μg band⁻¹ for MET and SPY, respectively. The second method was based on a reversed-phase liquid chromatographic separation of the cited drugs on a C-18 column (5 μm, 250 × 4.6 mm, i.d.). The mobile phase consisted of a mixture of phosphate buffer of pH 2.4 and acetonitrile (70:30, v/v). The separation was carried out at ambient temperature with a flow rate of 1.0 mL min⁻¹. Quantitation was achieved with UV detection at 232 nm based on peak area with linear calibration curves at concentration ranges 0.4–50.0 and 0.5–50.0 μg mL⁻¹ for MET and SPY, respectively. The proposed chromatographic methods were successfully applied to the determination of the investigated drugs in pharmaceutical preparations. Both methods were validated in compliance with ICH guidelines; in terms of linearity, accuracy, precision, robustness, limits of detection and quantitation and other aspects of analytical validation.

     

Tandem Use of Optical Sensing and Machine Learning for the Determination of Absolute Configuration,Enantiomeric and Diastereomeric Ratios,and Concentration of Chiral Samples

We have developed an optical method for accurate concentration, er, and dr analysis of amino alcohols based on a simple mix-and-measure workflow that is fully adaptable to multiwell plate technology and microscale analysis. The conversion of the four aminoindanol stereoisomers with salicylaldehyde to the corresponding Schiff base allows analysis of the dr based on a change in the UV maximum at 420 nm that is very different for the homo- and heterochiral diastereomers and of the concentration of the sample using a hypsochromic shift of another absorption band around 340 nm that is independent of the analyte stereochemistry. Subsequent in situ formation of Cu^II assemblies in the absence and presence of base enables quantification of the er values for each diastereomeric pair by CD analysis. Applying a linear programming method and a parameter sweep algorithm, we determined the concentration and relative amounts of each of the four stereoisomers in 20 samples of vastly different stereoisomeric compositions with an averaged absolute percent error of 1.7 %.     

Tandem Use of Optical Sensing and Machine Learning for the Determination of Absolute Configuration,Enantiomeric and Diastereomeric Ratios,and Concentration of Chiral Samples

We have developed an optical method for accurate concentration, er, and dr analysis of amino alcohols based on a simple mix‐and‐measure workflow that is fully adaptable to multiwell plate technology and microscale analysis. The conversion of the four aminoindanol stereoisomers with salicylaldehyde to the corresponding Schiff base allows analysis of the dr based on a change in the UV maximum at 420 nm that is very different for the homo‐ and heterochiral diastereomers and of the concentration of the sample using a hypsochromic shift of another absorption band around 340 nm that is independent of the analyte stereochemistry. Subsequent in situ formation of Cu^II assemblies in the absence and presence of base enables quantification of the er values for each diastereomeric pair by CD analysis. Applying a linear programming method and a parameter sweep algorithm, we determined the concentration and relative amounts of each of the four stereoisomers in 20 samples of vastly different stereoisomeric compositions with an averaged absolute percent error of 1.7 %.     

紫外联机卡尔曼滤波用于多组分混合物同时分析的研究

介绍了IBM PC/AT微机与DMS200UV/vis分光光度计联机系统的基本结构,利用这一联机系统,借卡尔曼滤波方法实现了2种多组分混合物体系的同时快速分析,结果令人满意.     

Numerical Method for Determination of Composition of Weak Acid Mixtures by Potentiometric Titration

An equation describing the state of weak acid mixtures was derived from the relationships between mole balance and charge balance. The equation was solved with numerical method and the compositions of the acid mixtures were determined. The advantages of this treatment were demonstrated by analyzing binary mixtures of chloroacetic, formic and acetic acids.     

Changes in the Enantiomeric Composition of Chiral Mixtures Upon Adsorption on a Non‐Chiral Surface

The adsorption of propylene oxide, a chiral molecule, on a Pt(111) single‐crystal surface was studied as a function of enantiomeric composition by temperature programmed desorption (TPD) and molecular beams. Two opposing trends were observed leading to variations in the enantiomeric excess (ee) of the chemisorbed layers with respect to the composition of the gas‐phase mixtures: a kinetic effect dominant during the initial uptake, with a preference toward the formation of enantiopure layers, and a steady‐state effect seen after approximately monolayer half‐saturation, at which point the preference is toward racemization. These effects may account for important phenomena such as the bias toward one chirality in biological systems and the selective crystallization of some chiral compounds, and may also be used in practical applications for chemical separations and catalysis.     

比值光谱一阶导数法同时测定苯酚和间苯二酚

以二元混合物的光谱除以其中某一组分的标准光谱而得到的比值光谱，对波长求导，可将重叠光谱分开而消除干扰，从而可方便的完成二组分混合体系中各组分的测定，     

Amperometric and Conductimetric Methods for Simultaneous Determination of Captopril and Bendroflumethiazide

Abstract

The mixture of captopril (antihypertensive) and bendroflumethiazide (diuretic) was assayed using conductimetric and amperometric methods. Each method was applied for the analysis of laboratory-made sample mixtures in authentic and dosage forms. For captopril, the amperometric and conductimetric methods gave mean percent recoveries of 100.2 ± 1.2 and 99.6 ± 1.2, respectively. These results have shown good agreement when compared with other methods in the literature. When applied to bendroflumethiazide the conductimetric method gave percent recovery of 98.5 ± 1.6 which agreed closely with the spectrophotometric pharmacopoeial method.

The pK₁ for captopril was determined potentiometrically at room temperature (25°C) in aqueous medium. The calculated value, based on Henderson equation was 3.78.     

比光谱-导数光度法同时测定铅、镉、汞

测定食品和环境中Pb~(2+)、Cd~(2+)、Hg~(2+)的含量是较常见的分析任务.光度法同时测定Pb~(2+)、Cd~(2+)、Hg~(2+)时,常因吸收峰重叠给测定带来困难.本文阐述了利用四(4三甲铵基苯基)卟啉(TAPP)对Pb~(2+)、Cd~(2+)、Hg~(2+)同时显色,采用KI、低聚合度聚乙烯醇(PVA)增敏、增溶,在吸收光谱严重重叠情况下,采用比光谱导数和零交点法,不经分离和掩蔽,用光度法同时测定Pb~(2+)、Cd~(2+)、Hg~(2+)的含量,Pb~(2+)、Cd~(2+)、Hg~(2+)的ε_(max)分别为ε_(481.5)=4.9×10~5、ε_(457)= 7.9×10~5、ε_(444.5)=8.1×10~4(L·mol~(-1)·cm~(-1)),Pb~(2+)、Cd~(2+)、Hg~(2+)的检出限分别为4μg/L、2μg/L和10μg/L.该方法计算简便、快速.     

比光谱-导数-紫外分光光度法同时测定水中苯酚和苯胺

1 引言 苯酚、苯胺共存时,它们的紫外吸收光谱彼此重叠。同时测定混合组分中的各个组分可以应用多波长测定吸光度,然后计算各组分含量,或用多波长线性回归-导数分光光度法。比值导数波谱法能够方便地排除干扰,已用于各种多组分的测定。本文用这种方法研究了苯酚、苯胺混合物的测定,结果满意。2 实验部分     

Enantiomeric and Diastereomeric Relationships of Ethylene Derivatives. Restructuring Stereochemistry by a Group-Theoretical and Combinatorial Approach

To restructure stereochemistry into a systematic format, enantiomeric and diastereomeric relationships have been investigated by using ethylene derivatives as examples in the light of a new group-theoretical and combinatorial approach. On one hand, enantiomeric relationship for ethylene derivatives has been characterized by means of a point group of order 8 (D _2h ), where chirality fittingness based on the sphericity concept has been applied to the enumeration of stereoisomers. On the other hand, diastereomeric relationship for ethylene derivatives has been examined by a permutation group of order 8 (S ₉ ^[4]), which is a subgroup of the symmetric group of order 4 (S ^[4]) and isomorphic to a point group D _2d . The subgroups of S ₉ ^[4] have been classified into stereogenic and astereogenic ones. A stereogenic subgroup corresponds to a pair of diastereomers, while an astereogenic subgroup is assigned to a self-diastereomer. The relationship between diastereomers and constitutional isomers have been also discussed.     

比值导数波谱法分析混合色素

本文叙述了比值导数波谱法的原理，该法以混合物的波谱除以干扰组分的标准波谱面得到比值波谱，以比值波谱对波长求导得到比值导数波谱，由此得到的波谱可完全消除干扰组分的吸光度贡献。采用此法能方便地对二组分混合体系进行分析，如选择合适的零交点，则可对二组分混合体系进行分析。利用此法对胭脂红、日落黄及柠檬黄三种色素的二组分及三组分混合体系进行了分析，均获较好的结果。