J.A. De Schutter

Stability study and quantitative determination of mebeverine hydrochloride in tablets by means of reversed-phase high-performance liquid chromatography

SummaryA rapid and specific reversed-phase high-performance liquid chromatographic method (RPHPLC) is described for the determination of mebeverine hydrochloride in tablets. Elution was performed on an octyl silane column with a methanol-water mixture (75-25), containing 0.05% hexylamine as silanol-blocking agent, adjusted to pH 5.0 with phosphoric acid. The method gave accurate, precise and reproducible results. The mean recovery of the drug from six synthetic tablet mixtures was 100.0% with a relative standard deviation (RSD) of 0.94%. In order to test the specificity of the method, the interference of the degradation compounds of mebeverine hydrochloride and of the intermediates from the synthesis was investigated. None of them did interfere. By means of mass spectrometry and UV-spectrophotometry, the degradation compounds of mebeverine were identified as veratric acid and as 4-|ethyl-[2-(4-methoxyphenyl)-1-methylethyl]amino| 1-butanol. The stability study proved that mebeverine hydrochloride is very stable in tablets; the tablets still contain more than 95% of the declared drug potency after storage for more than one year at 50°C.

Determination of S-carboxymethylcysteine in serum by reversed-phase ion-pair liquid chromatography with column switching following pre-column derivatization with o-phthalaldehyde

A method is described for the determination of S-(carboxymethyl)-l-cysteine in serum. After addition of S-(carboxyethyl)-l-cysteine as internal standard, both compounds are extracted into methanol, converted into fluorescent derivatives with o-phthalaldehyde and quantitatively determined by reversed-phase high-performance liquid chromatography. Chromatography of unwanted amino acid derivatives is avoided by column switching, thereby shortening analysis time and increasing column lifetime. The technique was applied in a study of the bioavailability of S-(carboxymethyl)-l-cysteine after oral administration to humans. The concentration-response curve was linear from 2 to 16 μg/ml; mean serum concentrations are reported.

Polar contributions of the stationary phase to the reversed-phase ion-pair high-performance liquid chromatographic separation of quaternary ammonium drugs.

The chromatographic reproducibility of a methodology, developed for the separation and determination of quaternary ammonium drugs by reversed-phase ion-pair column liquid chromatography, was studied. The results in terms of retention dependence on the residual silanol content of the octadecyl stationary phase and column aging were compared with those obtained with conventional separation techniques. By on-column silylation with N-trimethylsilylimidazole, it was demonstrated that eluents containing both amines and alkanesulphonates, beside a higher resolving power, provide reproducible separations which are far less dependent on the residual and generated silanol groups compared to those obtained with eluents containing only an organic amine.

On the problem of the purity of solvents in HPTLC

SummaryThe influence of stabilizers (2,6-di-tert-butyl-4-methylphenol and hydroquinone) and impurities in solvents on the reproducibility of the quantitative stability-indicating determination of mebeverine hydrochloride by means of high-performance thin-layer chromatography is reported.

Determination of oxybutinin chloride in pharmaceuticals by reversed-phase ion-pair liquid chromatography with two counter-ions in the eluent

A reliable stability-indicating method using reversed-phase ion-pair high-performance liquid chromatography for the determination of the anticholinergic drug oxybutinin chloride in pharmaceuticals is reported. Sample extraction is easy and fairly rapid and recovery and precision of the method are excellent. Due to the simultaneous use of an organic amine and of an alkanesulphonate in the mobile phase, good selectivity towards related (quaternary ammonium) anticholinergic drugs was obtained.

Simultaneous effects of amines and alkylsulphonates in reversed-phase ion-pair liquid chromatography - application to the separation of 2-imidazoline drugs

Abstract The reversed-phase liquid chromatographic separation of several pharmaceutically important 2-imidazoline derivatives using eluents containing both amines and alkylsulphonates, is described. The addition of N , N -dimethyloctylamine and sodium octanesulphonate to an acidic aqueous methanolic eluent, resulted in an eluent with much higher separation power than mobile phases containing only one modifier. The combined effect of the amine and of the alkylsulphonate enabled baseline (or nearbaseline) separations of all the 2-imidazolines studied. The use of such eluents is described in terms of efficiency, selectivity, peak symmetry and separation time and the mechanism of retention is discussed. Some separation examples are given to demonstrate the applicability of the developed technique in the quality control of these drugs in pharmaceuticals.

Gas chromatographic determination of parabens in various pharmaceutical dosage forms

SummaryA specific, sensitive and general applicabla gas chromatographic method is described for the determination of parabens in various liquid pharmaceutical preparations: propylparaben and butylparaben in a liquid antacid dosage form (I); methylparaben, ethylparaben and propylparaben in a syrup (II); methylparaben and propylparaben in a solution for injection (III). Each time one of the parabens is used as internal standard. The parabens are extracted with diethylether and derivatized by silylation. Different columns are used for the analysis of the parabens: 3% SE-30 column, a 3% QF-1 column for different selectivity, a 2% OV-1 column for isothermal operation.Special attention is attributed to the standard: the parabens are dissolved in a minimal amount of 0.1 M sodium hydroxide and extracted in the same way as the pharmaceutical dosage form.

Analysis of propantheline bromide and related quaternary ammonium drugs by reversed-phase, ion-pair liquid chromatography with two counterions in the eluent

SummaryThe addition of appropriate concentrations of an organic amine and an alkylsulphonate to the mobile phase in reversed-phase, ion-pair liquid chromatography can introduce unique selectivity in to the chromatographic system allowing separation of complex mixtures of basic, acidic and neutral compounds. As an example, the methodology for a specific stability-indicating determination of propantheline bromide, a quaternary ammonium anticholinergic agent, on several reversedphase stationary phases, was developed. The retention mechanism was studied and it was concluded that both ion-interaction processes and ion-exchange processes were involved in the separation technique developed with two counterions of opposite charge in the eluent.

Reversed-phase ion-pair liquid chromatography of some quaternary ammonium drugs☆

The resolving power of a reversed-phase liquid chromatographic method that makes use of a mobile phase system with two counter-ions of opposite charge (N,N-dimethyloctylamine and sodium octanesulphonate) for the separation of quaternary ammonium drugs, is compared with that obtained using more traditional ion-pairing systems. Efficient, selective and well-resolved separations could only be obtained by the combined effects of the eluent modifiers.

Separation and determination of isopropamide iodide in pharmaceutical formulations by reversed-phase ion-pair high-performance liquid chromatography

Abstract A stability-indicating determination for isopropamide iodide, an anticholinergic quaternary ammonium drug, in several pharmaceutical dosage forms by reversed-phase ion-pair liquid chromatography is reported. The use of eluents containing both an amine as well as an alkylsulphonate proved to be very efficient for separating and determining quaternary ammonium drugs and related other basic drugs: adequate selectivity, excellent peak shape and good reproducibility (coefficient of variation, 1–2%) were obtained in a short analysis time.