Short communication

Ion-selective electrode for serum bromide assay in patients with epilepsy

The purpose of the present work was the development and validation of a simple, rapid and reliable method for direct bromide quantification in serum based on capillary electrophoresis (CE). The analysis was carried out with an automated capillary electropherograph. Analytical conditions were as follows. Capillary: uncoated fused silica, effective length 50 cm, internal diameter 50 μm; voltage: 20 kV in reverse polarity mode; temperature: 25 °C; running buffer: 90 mmol/L sodium tetraborate decahydrate and 10 mmol/L NaCl, pH 9.24; detection: direct UV absorption at 200 nm; sample treatment: dilution of serum 1:10 with the internal standard solution (2 mmol/L thiocyanate). Under the described conditions, bromide ions and internal standard were baseline separated in 7 min. No interferences from other serum components were observed. The analytical sensitivity was characterized by a LOD: 0.05 mmol/L and a LOQ of 0.1 mmol/L. Excellent linearity was verified in the range from 2.5 to 60 mmol/L [y = 0.0746x − 0.0372; R² = 0.9995 (x = bromide concentration; y = bromide peak area/internal standard (I.S.) peak area)]. Quantitative imprecision in intra-day (n = 7) and day-to-day (n = 7) experiments was always within R.S.D. values <2%. Recovery was quantitative throughout the range of linearity of the method. Clinical cases of infants undergoing potassium bromide therapy for refractory epilepsy were analyzed with results in agreement with literature data. On the basis of these considerations, capillary electrophoresis can be proposed as the method of choice for bromide analysis in serum samples, especially for therapeutic drug monitoring purposes.

A novel bromide ion-selective PVC membrane sensor based on 2,3,10,11-tetraphenyl-1,4,9,12-tetraazacyclohexadeca-1,3,9,11-tetraene zinc(II)complex (I) as carrier has been developed. The electrode exhibited wide working concentration range 2.2 × 10⁻⁶ to 1.0 × 10⁻¹ M and a limit of detection as 1.4 × 10⁻⁶ M with a Nernstian slope of 59.2 ± 0.5 mV per decade. The response time of electrode was 20 s over entire concentration range. The electrode possesses the advantages of low resistance, fast response and good selectivities for bromide over a variety of other anions and could be used in a pH range of 3.5–9.5. It was successfully used as an indicator electrode in the potentiometric titration of bromide ions with silver ion and also in the determination of bromide in real samples.

Bromides are no longer a mainstay of epilepsy therapy because of the significant toxicity associated with their use and the availability of safer agents. However, bromides occasionally find a niche in the treatment of patients with refractory seizures, particularly in pediatrics. When the decision to utilize this therapy is made, the clinician may be frustrated by the lack of concise, current information regarding bromides. This review provides an update on the mechanism of action, efficacy, pharmacokinetics, dose, and adverse effects of bromides.

A flow injection system was constructed using a bromide-selective electrode and used to determine serum bromide in patients with epilepsy. A 10-μl serum sample was injected into a carrier stream flowing at 0.12 ml min⁻¹. Potential changes and bromide concentrations were linearly related in the range 3–50 mM. The lower limit of detection for serum bromide was 1 mM and this electrode sensitivity spanned the entire concentration range required for bromide therapy (9–24 mM). The results compared favourably with those obtained by colorimetry.

Free disopyramide levels in blood serum, the monitoring of which is especially effective for antiarrhythmic therapy, were determined in situ using a disopyramide-sensitive membrane electrode. Sodium tetrakis[3,5-bis(2-methoxyhexafluoro-2-propyl)phenyl]borate was incorporated as the ion-exchanger and 2-fluoro-2′-nitrodiphenyl ether as the solvent mediator in a poly(vinyl chloride) membrane matrix to form the electrode. The lower limit of the detection for free disopyramide in serum was 0.8 μM. The free disopyramide concentrations measured by the ion-selective electrode agreed well with those determined by an established fluorescence polarization immunoassay that requires an additional ultrafiltration procedure to remove disopyramide bound to serum protein.

A salicylate-selective membrane electrode made with heptyl-4-trifluoroacetylbenzoate as a neutral carrier was successfully applied for the determination of salicylate in blood serum. This procedure is advantageous because the free concentration of the drug in serum can be determined without sample preparation. The free salicylate concentrations determined by the ion-selective electrode compared to those obtained by conventional colorimetry gave a linear correlation coefficient 0.997 in the salicylate concentration range 0.1–2.5 mM.