Mathematical representation of electrophoretic mobility of basic drugs in ternary solvent buffers in capillary zone electrophoresis

doi:10.1016/S0021-9673(03)00387-X

Journal of Chromatography A

Volume 994, Issues 1–2, 25 April 2003, Pages 191-198

https://doi.org/10.1016/S0021-9673(03)00387-X Get rights and content

Abstract

The electrophoretic mobilities of two β-blocker drugs, i.e., labetalol and atenolol, have been determined in a mixed solvent background electrolyte system containing sodium acetate+acetic acid as buffering agent and different volume fractions of water, methanol and ethanol using capillary electrophoresis. The produced data and three other sets collected from a recent work are employed to study the accuracy and prediction capability of a mathematical model to calculate the electrophoretic mobility with respect to the volume fractions of the solvents in the mixture. The results show that the proposed model is able to correlate/predict the mobility within an acceptable error range and it is possible to use the model in industry to achieve the optimum solvent composition for the buffer where using a ternary solvent system is required. The average percentage deviations (APDs) obtained for correlated and predicted data points are 0.71–2.48 and 1.72–4.39%, respectively. The accuracy of the proposed model is compared with that of a mixture response surface method and the results show that the proposed model is superior from both correlation and prediction points of view. The possibility of calculation of the mobility of chemically related drugs in water–methanol–ethanol mixtures using the proposed model is also shown and the produced prediction APD is ∼8%.

Introduction

Capillary electrophoresis (CE) is a technique that has become a well established method in the separation of a variety of compounds of pharmaceutical interest. Most of the work with CE has involved aqueous running buffer, however organic solvents have been used in conventional electrophoresis and isotachophoresis for many years. The area of mixed solvent background electrolytes (BGEs) has a lot of potential in CE. This area exploits the vastly different physicochemical properties of organic solvents to control the electroosmotic flow (EOF) and analyte migration [1], [2], [3]. It is not a novel technique for binary, ternary and even quarternary mobile phases that have been used in high-performance liquid chromatography (HPLC) for many years, but it is only recently that binary and ternary BGEs have been explored in CE. One example of the use of a binary BGE is the separation of paraquat and diquat herbicides in water and acetonitrile mixtures [4]. Binary BGEs are also employed in other validated CE methods [5], [6], [7], [8], [9], [10], [11]. Less work has been performed on ternary solvents in the BGE. A simple CE separation of four structurally related prostaglandins in a running buffer containing acetonitrile, methanol and water (total organic solvents=80%) has been reported [12]. The authors explained that the binary mixtures of methanol and acetonitrile are not able to resolve all the prostaglandins studied and this could be achieved by addition of 20% water to methanol–acetonitrile (75:25, v/v). Under optimised conditions, the method was then validated to international conference on harmonization (ICH) guidelines. In addition, ternary solvent BGEs are used in reported CE methods [13], [14].

It is generally difficult to predict the effects of organic solvents on the electrophoretic mobility of analytes and electroosmotic flow without using experimental mobility data. Increasing the number of organic solvent components in the BGE leads to an increase in the number of experiments for optimisation, which is generally performed by trial and error. Thus, the use of a mathematical equation to reduce the time spent on optimisation is of utmost importance and interest, especially to the pharmaceutical industry who are forever searching for reductions in method development times.

This work is an extension of previous work [15], [16] which have highlighted the possibility of minimising the number of experiments to predict the mobility of drugs in mixed solvent systems by the use of the mathematical models. To show the applicability of the proposed model on real data the electrophoretic mobility of two β-blocker drugs, i.e., labetalol and atenolol, have been determined in a ternary solvent BGE. In addition, three other mobility data sets for practolol, timolol and propranolol [17] have been employed as further experimental data sets. The accuracy of the proposed model is compared with that of a previous mixture response surface model [17] using average percentage deviation (APD) and also distribution of individual percentage deviations as comparison criteria. The prediction capability of the model is evaluated by using a minimum number of data points for model training and predicting the other data points. Also, the proposed model is employed to predict the mobility of labetalol and atenolol in ternary solvent acetate buffer using experimental points of three other β-blocker drugs in the same mixed solvent buffer which provide a pure predictive equation.

Section snippets

Theoretical treatment

In our earlier work [15], a solution model has been proposed to compute the electrophoretic mobility of analytes in binary solvent electrolyte systems. The model is: $ln μ_{m} =f_{1} ln μ_{1} +f_{2} ln μ_{2} +f_{1} f_{2} A_{0} +A_{1} f_{1} −f_{2}$ where μ is the electrophoretic mobility, subscripts m, 1 and 2 refer to mixed solvent, solvents 1 and 2, respectively, f is the volume fraction of the solvent in the mixed solvent system and A₀−A₁ are the model constants calculated by a least-squares analysis. It has been shown that the

Instrumentation

All experiments were performed using a P/ACE system 5510 series instrument with Beckman P/ACE software (Beckman Instruments Europe, High Wycombe, UK). The fused-silica capillary was purchased from Composite Metal Services (Hallow, UK) and was 37 cm (30 cm to the detector)×75 μm I.D. The temperature of the capillary was kept at 25.0 °C using a liquid coolant. Samples were injected by low pressure (0.5 p.s.i.) for 2 s and analytes were detected at 214 nm (1 p.s.i.=6894.76 Pa). The applied voltage

Results and discussion

Table 1 shows the experimental effective mobility (±SD) of labetalol and atenolol in ternary solvents. As a general pattern, the higher the water volume fractions in the mixtures, the higher the mobility as the maximum mobility has been observed in pure aqueous buffer. With higher ethanol volume fractions in the mixtures the lower the mobility has been observed and the pure ethanolic buffer moves the analytes with the least speed. These observations could be confirmed considering the lower

Acknowledgements

The authors would like to thank the Australian Department of Education, Training and Youth Affairs and the University of Sydney for providing the IPRS and IPA scholarships. The authors also acknowledge Professor E. Kenndler, University of Vienna, Austria for his helpful comments.

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Mathematical representation of electrophoretic mobility of basic drugs in ternary solvent buffers in capillary zone electrophoresis

Abstract

Introduction

Section snippets

Theoretical treatment

Instrumentation

Results and discussion

Acknowledgements

J. Chromatogr. A

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