E. La Porta

Potentiometric titration of thiols, cationic surfactants and halides using a solid-state silver—silver sulphide electrode

A rugged, low resistance silver-silver sulphide solid-state electrode for determining pharmaceuticals as authentic samples or in dosage forms by potentiometric titration is described. Sodium tetraphenylborate, mercury(II) acetate and silver nitrate (0.01) M were employed as titrants in the analysis of cationic surfactants (cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride and chlorhexidine salts), antithyroid drugs (methimazole and propylthiouracil) or sodium halides respectively.

Experimental design strategies in the optimization and robustness testing of adsorptive stripping voltammetric conditions for kynurenic acid determination

Experimental design was used for the optimization and robustness testing of an adsorptive stripping voltammetric procedure for kynurenic acid determination. The optimization of the peak height response proceeded through a screening phase (D-optimal design strategy) followed by a response surface study (Doehlert design) applied to the variables pH, pulse amplitude and stirring rate. An interaction between pH and stirring rate was pointed out. The optimized method was validated and the variation of factors that was expected to occur in practice was simulated in a robustness test. A composite fractional matrix for the evaluation of method robustness was used and pH emerged as the only critical factor. The linear range found applying the optimized conditions was 2.5 x 10(-9) to 2.5 x 10(-7) M and the calculated limit of detection was 1.72 x 10(-9) M.

Optimization and validation of a CZE method for rufloxacin hydrochloride determination in coated tablets.

A simple and rapid capillary electrophoresis method with UV detection was developed and validated for the determination of rufloxacin hydrochloride in coated tablets. An experimental design strategy (Doehlert design and desirability function) allowed the analytical parameters to be simultaneously optimized in order to determine rufloxacin hydrochloride with high peak area/migration time ratio, good efficiency and short analysis time. Optimized analyses were run using boric acid 0.10 M adjusted to pH 8.8 as BGE and setting voltage and temperature at 18 kV and 27 degrees C, respectively. Pefloxacin mesylate was used as internal standard and run time was about three minutes. The method was validated for the drug substance and the drug product according to the ICH3 guidelines. Robustness was tested by experimental design using an eight-run Plackett-Burman matrix.

Simultaneous determination of naphazoline and diphenhydramine hydrochlorides in nasal drops by second-order derivative UV spectroscopy

Abstract A second-derivative spectroscopic method for the simultaneous determination of naphazoline hydrochloride and diphenhydramine hydrochloride in nose drops was developed. Solutions of this drug combination in 0.1 M hydrochloric acid were analyzed by measurement of the amplitudes of, respectively, the positive peak at 288 nm with respect to the negative peak at 282 nm, and the negative peak at 249 nm with respect to the base line. The method allows the specific, rapid and accurate determination of the binary mixture in the tested concentration range of 1–5 μg/ml for naphazoline, and 10–50 μg/ml for diphenhydramine.

Use of the silver electrode in the potentiometric determination of quaternary ammonium compounds

A reduced-scale direct potentiometric titration method is proposed for determining medicinally important quaternary ammonium compounds alone or in pharmaceutical formulations. An automatic titrator is employed with a silver-mercury(I) sulphate electrode system. The procedure reported provides a precise, accurate and rapid analysis when 0.03–0.13 g l–1 of compound is present in aqueous solution.

Chlorhexidine loss from simulated contact lens solutions stored in glass and plastic packages.

A storage test on chlorhexidine gluconate (0.004%) in aqueous or simulated contact lens solutions, conducted for 6 months in various containers, suggested [l] that loss of activity by a surface adsorption process was occurring. It has been reported [2] that contact lens solutions containing chlorhexidine gluconate (0.~5%) stored at room temperature in the dark for 6 months in polypropylene, polyethylene, and amber and clear glass, showed an antiseptic loss of 4-10% in plastic containers and, unexpectedly, of 16% and 25% in amber and clear glass respectively. However, the type of glass employed was not stated. More recently [3], storage experiments on ophthalmic drops containing benzalkonium chloride or chlorhexidine acetate indicated no adsorption by glass or ~lyethylene containers. The calorimetric method [4] used in this case for assaying the preservatives has been criticized as yielding large errors [5] and as unsuitable for the determination of chlorhexidine salts [6]. Chlorhexidine gluconate (O.OOl-0.006%), combined with benzalkonium chloride or thiomersal, is widely employed as a preservative in contact lens solutions. These solutions are ~mmonly packaged in polyolefin containers and many regulatory authorities demand that there should be no container-preservative interaction. Recently the present workers described [6] a rapid and reliable calorimetric method for determining chlorhexidine gluconate in commercial contact lens solutions through the formation of a stable ion-pair with methyl orange. The ion pair can be extracted with chloroform without interference from other ingredients or from 4-chloroaniline, the main breakdown product of chlorhexidine. The present paper reports the application of

Determination of benzalkonium chloride in contact lens solutions by positive-ion fast atom bombardment mass spectrometry☆

Under positive-ion fast atom bombardment (FAB) mass spectrometric conditions, benzalkonium chloride (BAK) afforded intense peaks at m/z 304 and 332, corresponding to the intact cations [M--Cl]+ of C12 and C14 homologues, respectively. The use of benzethonium chloride as an internal standard and thioglycerol as a FAB matrix allowed the direct and specific determination of the BAK content (0.004-0.020%) in commercial hard contact lens solutions through the individual assay of the two alkyl homologues. A linear relationship between the homologue concentration and the peak-area ratio was observed over the concentration range 3-180 micrograms ml-1.

Differential-pulse adsorptive stripping voltammetry of chlorhexidine

Chlorhexidine gluconate was shown to adsorb onto a hanging mercury drop electrode and to be amenable to quantification by adsorptive stripping voltammetry. A sensitivity of 1 × 10–7 mol dm–3 was easily achieved by simply immersing the electrode in a stirred solution (pH 9.7 ammonia-ammonium acetate buffer) of the drug for a fixed time (60 s), at a suitable potential (0.0 V versus Ag–AgCl), and then stripping cathodically in the differential-pulse mode. The stripping peak potential was –1.53 V. Cyclic voltammetry was used to test the interfacial and redox behaviour. Chlorhexidine gluconate was assayed in mouthrinse and contact lens solution dosage forms.

Differential pulse polarographic determination of total benzophenantridinium alkaloids in Sanguinaria extract-based oral rinses

A differential pulse polarographic method was developed for the determination of total benzophenantridinium alkaloids in Sanguinaria canadensis extract-based oral rinses without prior extraction procedures, Mcllvaine buffer (pH 3.4) being employed as the supporting electrolyte. The electrochemical reduction involves the transfer of one electron and potential of the single peak occurs between − 0.39 and −0.44 V vs Ag/AgCl as a function of the different relative percentage of benzophenantridinium alkaloids. The alkaloid amount was expressed as chelerythrine chloride and calculated by means of a calibration graph. A column Chromatographie procedure to obtain chelerythrine chloride reference standard is described. Common oral rinse excipients and zinc ions were found not to interfere.