Chiral separation of the four stereoisomers of a novel antianginal agent using a dual cyclodextrin system in capillary electrophoresis

Reported here is an analytical method enabling the stereochemical resolution of a new antianginal compound possessing two stereogenic centers, leading to four stereoisomers. Only one of these isomers is currently under development as a novel antianginal agent and consequently, the other three isomers are considered as unwanted chiral impurities. Therefore, an enantioselective method is required in order to check its enantiomeric purity. This paper presents a method exploiting the high efficiency of capillary electrophoresis and the complexing properties of cyclodextrins to achieve the separation of the four stereoisomers of this weakly basic compound (pKa = 7.4). For this purpose, the combination of a neutral cyclodextrin, hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD), and an anionic cyclodextrin, carboxymethyl-beta-cyclodextrin (CM-beta-CD), was added to the separation buffer running in an uncoated silica capillary. After selection of the suitable cyclodextrin system, satisfactorily separation conditions were as follows: 30 mM phosphate buffer (pH 6.4) containing 10 mM of HP-gamma-CD and 10 mM of CM-beta-CD, running voltage +30 kV. The resulting run time and resolutions were respectively about 17 min and between 1.95 and 2.84. Linearity curves (0.993 < r2 < 0.998) are also shown.     

Comparison of dephasing times for vibrational and rotational coherent anti-Stokes Raman scattering: implications for velocimetry

Time-domain coherent anti-Stokes Raman scattering experiments have been carried out by probing vibrational and pure rotational lines of nitrogen in the Doppler broadened regime. The theoretical analysis of the transient responses outlines the role of the geometrical effects. For pure rotational CARS, it is shown that the main contribution to the dephasing of the Raman coherence results from the change in direction between the pump and anti-Stokes wave vectors whereas the difference between the modulus of these two wave vectors accounts for dephasing in vibrational CARS. Furthermore, we demonstrate that the range of operation of time-domain CARS velocimetry is extended by probing pure rotational lines. The predictions are validated by experiments which are performed both in a static gas cell and in a Mach 10 supersonic flow. Received: 30 March 2000 / Revised version: 9 June 2000 / Published online: 13 September 2000     

Temporal behavior of a high repetition rate infrared optical parametric oscillator based on periodically poled materials

The temporal behavior of a nanosecond pulsed singly resonant periodically poled lithium niobate optical parametric oscillator has been studied both theoretically and experimentally. Taking into account the cylindrical symmetry of the system, a numerical model based on the Hankel transform has been developed. Good agreement is obtained between experiment and simulation. Moreover, the computation time is reduced roughly by a factor of 60 compared to the usual simulation software. Received: 23 April 2001 / Published online: 19 September 2001     

A Convenient Approach to Simultaneous Analysis of a Pharmaceutical Drug and Its Counter-Ion by CE Using Dual-Opposite End Injection and Contactless Conductivity Detection

Capillary electrophoresis (CE) coupled to a capacitively coupled contactless conductivity detector (C⁴D) was used for the determination in a single analysis of a pharmaceutical drug and its counter-ion. Dual-opposite end injection (DOI) was used to introduce hydrodynamically the analytes at each end of the capillary. No modification of the commercial apparatus is required. After applying the voltage, the cations and anions migrate from each end of the capillary in opposite directions toward the detector placed near the cathode outlet. The electrophoretic conditions were initially developed with three test drugs (chlorpheniramine maleate, metoprolol tartrate, clomiphene citrate) and then applied to two Vinca alkaloids (catharanthine sulfate, vinorelbine ditartrate). The 10 mM histidine–50 mM acetic acid buffer (pH 4.1)–methanol 90:10 (v/v) electrolyte was suitable for the analysis of these high or medium mobile anions by CE–C⁴D due to its low conductivity background and high buffer capacity. Finally, the CE procedure developed was successfully validated for catharanthine sulfate. The method developed herein is fast (<10 min) and accurate (repeatability on migration time < 0.6% and peak areas < 1.3%, n = 6).

     

Chiral analysis of milnacipran by a nonchiral HPLC--circular dichroism: improvement of the linearity of dichroic response by temperature control

The determination of the enantiomeric excess (e.e.) of a basic drug has been investigated in LC using a nonchiral stationary phase and a circular dichroism (CD) detector in order to avoid expensive chiral columns. The CD detector records both dichroic (Deltaepsilon) and UV (epsilon) signals at the same wavelength and calculates the anisotropy factor (g=Deltaepsilon/epsilon), which is linearly related to the e.e. The enantiomeric and chemical composition of a chiral drug can be simultaneously determined on a nonchiral HPLC support. However, the g factor from the CD signal is temperature dependent. Indeed, the temperature has an influence on the stability of the CD signal and the linear regression between g factor and the e.e. of 1R,2S-enantiomer. So, a decrease in temperature gives rise to an improvement of the above-mentioned linearity correlation. After optimization of chromatographic parameters (porous graphitic carbon-based column, methanol/ phosphate buffer as mobile phase) and selection of CD wavelength, a linear regression of g factor versus e.e. of 1R,2S-enantiomer was obtained at temperature-controlled CD detection and an LOQ of 94% was found. The enantiomeric composition of milnacipran was determined with good accuracy.