Jos Hoogmartens

Quantitative analysis of quaternary ammonium antiseptics using thin-layer densitometry

A thin-layer chromatography method for quantitative analysis of quaternary ammonium antiseptics is described. Silanized silica gel was used as the stationary phase. The mobile phase consisted of methanol-25% (m/v) sodium acetate solution-acetone (65:35:20). The method is able to separate the chain homologues of benzalkonium chloride, cetylpyridinium chloride and cetrimide. Detection was performed using a colour reaction with potassium triiodide solution. The different homologues were quantified using UV densitometry at 400 nm. A number of commercial samples was analysed using this method. From the results it appears that it is worthwhile to have a limit test for the composition of quaternary ammonium antiseptics in pharmacopoeial monographs, the more so as the antibacterial activity depends on it.

Impurity Profiling of Dirithromycin by Liquid Chromatography Coupled to Electrospray Ionization Mass Spectrometry

The aim of this study was to characterize as much as possible the unknown peaks in the chromatogram obtained with a non-volatile LC-UV system, which was published earlier for the separation of dirithromycin and its related substances. For this purpose, each peak eluting from the non-volatile system was collected and transferred to a MS, after performing a desalting process. The desalting procedure uses a XTerra RP C18 column (250 mm x 4.6 mm, 5 µm) and two mobile phases consisting of a mixture of water / 0.1% (v/v) formic acid and a mixture of acetonitrile / 0.1% (v/v) formic acid, respectively. Mass spectral data were acquired on an LCQ ion trap mass spectrometer equipped with an electrospray ionization source (ESI), operating in the positive ion mode. In addition to the thirteen already known compounds, seven new compounds were elucidated. Five impurities showed modifications at the amino group of the desosamine molecule, one an alteration at position C-9 and one a modification at position C-13 of the macrolide ring.

CHEMICAL STABILITY AND COMPATIBILITY STUDY OF VANCOMYCIN FOR ADMINISTRATION BY CONTINUOUS INFUSION IN INTENSIVE CARE UNITS

In this study, various analytical techniques were applied in order to investigate the feasibility of continuously infusing vancomycin in intensive care units. First, the chemical stability of a 40 mg/mL vancomycin solution in normal saline was studied. The stability study included pH measurement, visual inspection, UV spectrophotometry, and assay by capillary electrophoresis. Subsequently, physical and chemical compatibility of vancomycin with five commonly co-administered drugs was evaluated. Physical compatibility tests consisted of pH measurement, visual inspection, and nephelometry. Physically compatible drugs were further assessed for chemical compatibility with vancomycin, by determining the vancomycin content in mixed samples using capillary electrophoresis. No changes in physical characteristics of the vancomycin solution were observed during 24 hours. The content of vancomycin remained higher than 90% of the nominal concentration throughout the stability study. Addition of sodium valproate and dipotassium clorazepate to the vancomycin solution resulted in precipitation. Vancomycin was physically compatible with amiodarone, piritramide and midazolam, respectively. Furthermore, capillary electrophoretic analysis revealed no decrease in vancomycin content upon mixing with physically compatible drugs. In conclusion, a 40 mg/mL vancomycin solution was proven to be stable and compatible with midazolam, piritramide, and amiodarone. Sodium valproate and dipotassium clorazepate, however, were physically incompatible with vancomycin.

Determination of the stability of tetracycline suspensions by high performance liquid chromatography

High performance liquid chromatography was used to examine the stability of tetracycline suspensions, prepared according to the Formulary of the Dutch Pharmacists and the National Formulary v (Belgium). The influence of the nature of the buffer salt, of the pH, and of the temperature and time of storage are discussed. At slightly acid pH (4 to 5.5) and at room temperature suspensions are stable for at least three months.