W. Van den Bossche

Simultaneous determination of hydrochlorothiazide and several angiotensin-II-receptor antagonists by capillary electrophoresis.

We have investigated the capability of the capillary zone electrophoretic (CZE) and micellar electrokinetic capillary chromatographic (MEKC) methods to simultaneously separate hydrochlorothiazide and six angiotensin-II-receptor antagonists (ARA-IIs): candesartan, eprosartan mesylate, irbesartan, losartan potassium, telmisartan, and valsartan. The CZE and MEKC methods are suitable for the qualitative and quantitative determination of combined HCT/ARA-IIs in pharmaceutical formulations. Depending on the ARA-II, at least one of the two methods can be used for each combination. The two methods have been validated in terms of their linearity of response, reproducibility, and accuracy.

The qualitative and quantitative determination of quinolones of first and second generation by capillary electrophoresis.

Capillary electrophoresis (CE) was applied to the study of 10 quinolones of first and second generation--nalidixic acid, oxolinic acid, pipemidic acid, cinoxacin, norfloxacin, ciprofloxacin, ofloxacin, pefloxacin, fleroxacin, and flumequine. Separation was performed on a fused silica capillary (75 microm-60 cm) using a phosphate buffer (pH 7.0, 125 mM). Detection was at 214 nm. Only norfloxacin and ciprofloxacin cannot be separated in this way. Because of the specificity of the method, the identification of the individual quinolones by their migration time was possible. The same system has been applied for the quantitative determination of quinolones in tablets and capsules. Excipients do not adversely affect the results. Some parameters (linearity, precision, accuracy) were validated. Especially the possibility of simultaneous quantification and identification of the active ingredient in the finished product is very attractive.

Optimization and validation of a capillary zone electrophoretic method for the analysis of several angiotensin-II-receptor antagonists

We optimized a capillary zone electrophoretic method for separation of six angiotensin-II-receptor antagonists (ARA-IIs): candesartan, eprosartan, irbesartan, losartan potassium, telmisartan, and valsartan. A three-level, full-factorial design was applied to study the effect of the pH and molarity of the running buffer on separation. Combination of the studied parameters permitted the separation of the six ARA-IIs, which was best carried out using 60 mM sodium phosphate buffer (pH 2.5). The same system can also be applied for the quantitative determination of these compounds, but only for the more soluble ones. Some parameters (linearity, precision and accuracy) were validated.

Simultaneous determination of hydrochlorothiazide and several inhibitors of angiotensin-converting enzyme by capillary electrophoresis.

A capillary electrophoresis method was developed for the simultaneous determination of hydrochlorothiazide and several angiotensin-converting enzyme (ACE) inhibitors: enalapril, lisinopril, quinapril, fosinopril, ramipril, and cilazapril. The most critical parameter is the pH of the running buffer. Separation was performed on a fused-silica capillary (52 cm total length x 75 microm I.D.) using a sodium phosphate buffer (pH 7.25; 100 mM). The method was successfully applied to the quantitative determination of these compounds in their corresponding pharmaceutical formulation. The method was validated in terms of linearity of response, reproducibility and accuracy.

Optimization and validation of a micellar electrokinetic chromatographic method for the analysis of several angiotensin-II-receptor antagonists

We have optimized a micellar electrokinetic capillary chromatographic method for the separation of six angiotensin-II-receptor antagonists (ARA-IIs): candesartan, eprosartan mesylate, irbesartan, losartan potassium, telmisartan, and valsartan. A face-centred central composite design was applied to study the effect of the pH, the molarity of the running buffer, and the concentration of the micelle-forming agent on the separation properties. A combination of the studied parameters permitted the separation of the six ARA-IIs, which was best carried out using a 55-mM sodium phosphate buffer solution (pH 6.5) containing 15 mM of sodium dodecyl sulfate. The same system can also be applied for the quantitative determination of these compounds, but only for the more stable ARA-IIs (candesartan, eprosartan mesylate, losartan potassium, and valsartan). Some system parameters (linearity, precision, and accuracy) were validated.

The determination of non-steroidal antiinflammatory drugs in pharmaceuticals by capillary zone electrophoresis and micellar electrokinetic capillary chromatography

Ibuprofen, indomethacin, ketoprofen, piroxicam and diclofenac have been quantified in dragees, suspension, suppositories, capsules, injection solutions and tablets by capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MEKC). The experiments were performed without specific sample pretreatment. The reproducibility of the method was investigated. Good quantitation was obtained in short analysis times. CE and MEKC are found to offer a good alternative to conventional HPLC methods.

Determination of captopril and its degradation products by capillary electrophoresis

Captopril, an antihypertensive agent, and its degradation products have been quantified in pharmaceutical formulations by capillary zone electrophoresis (CZE). A method using cetyltrimethylammonium bromide (CTAB) added to a sodium phosphate buffer (pH 5.5; 100 mM) as running buffer and using N-acetyl-L-tyrosine as an internal standard has been developed and validated for the quantitative determination of captopril in tablets. The method is an indicator of compound stability and can also be applied to the purity control of the raw material and for the determination of the degradation products. For this purpose, salicylic acid is used as an internal standard.

Optimization of capillary electrophoretic separation of several inhibitors of the angiotensin-converting enzyme.

Capillary electrophoretic separation of eight inhibitors of the angiotensin-converting enzyme, viz., enalapril, lisinopril, quinapril, fosinopril, perindopril, ramipril, benazepril and cilazapril, was investigated with respect to the following parameters: pH of the running buffer, organic modifiers and surfactants. The most critical parameter is the pH of the running buffer. The addition of sodium dodecyl sulfate had a negative influence on the peak symmetry, and selectivity was not improved. The separation of the eight compounds can be performed by means of two phosphate buffers (each 100 mM) at pH 7.0 and pH 6.25, respectively. This combination is necessary for the selective identification of structurally related substances because of their similar pKa values.

The quantitative determination of several inhibitors of the angiotensin-converting enzyme by CE

Capillary electrophoresis (CE) was applied to the study of several inhibitors of the angiotensin-converting enzyme. Separation of the compounds was performed by means of two phosphate buffers (each 100 mM) at pH 7.0 and 6.25, respectively [S. Hillaert, W. Van den Bossche, J. Chromatogr. A, 895 (2000) 33-42.]. Due to the highest selectivity of the first mentioned running buffer, the same system has been applied for the quantification of enalapril, lisinopril, quinapril, fosinopril, perindopril and benazepril in their corresponding pharmaceutical formulation. Especially, the possibility of simultaneous identification and quantification of the active ingredient in the finished product is very attractive. Excipients do not adversely affect the results. This paper deals with the validation of some parameters of the quantitative analysis: linearity, precision, accuracy and robustness.

Optimisation by experimental design of a capillary electrophoretic method for the separation of several inhibitors of angiotensin-converting enzyme using alkylsulphonates.

A statistical experimental design was used to optimise a capillary electrophoretic separation method for eight inhibitors of the angiotensin-converting enzyme: enalapril, lisinopril, quinapril, fosinopril, perindopril, ramipril, benazepril, and cilazapril. Because a free solution capillary electrophoresis system did not achieve a complete separation of these eight compounds in one run, the usefulness of alkylsulphonates as ion-pairing agents was investigated. After preliminary investigations to determine the experimental domain and the most important factors, a three-level full-factorial design was applied to study the impact of the pH and the molarity of the ion-pairing agent on the separation. Improved separations were obtained suggesting a favourable effect of ion-pairing interactions between analytes and the additive; however, it remained impossible to separate them all in one run. A combination of two systems was still necessary for the selective identification of these structurally-related substances.