A Robust Static Headspace GC-FID Method to Detect and Quantify Formaldehyde Impurity in Pharmaceutical Excipients.

Formaldehyde is a highly reactive impurity that can be found in many pharmaceutical excipients. Trace levels of this impurity may affect drug product stability, safety, efficacy, and performance. A static headspace gas chromatographic method was developed and validated to determine formaldehyde in pharmaceutical excipients after an effective derivatization procedure using acidified ethanol. Diethoxymethane, the derivative of formaldehyde, was then directly analyzed by GC-FID. Despite the simplicity of the developed method, however, it is characterized by its specificity, accuracy, and precision. The limits of detection and quantification of formaldehyde in the samples were of 2.44 and 8.12 µg/g, respectively. This method is characterized by using simple and economic GC-FID technique instead of MS detection, and it is successfully used to analyze formaldehyde in commonly used pharmaceutical excipients.

Development of a validated HPLC method for the separation and analysis of a Bromazepam, Medazepam and Midazolam mixture.

The purpose of this work was to develop a rapid, sensitive and validated HPLC method for the separation and analysis of a Bromazepam, Medazepam and Midazolam mixture. The three benzodiazepine compounds were separated on a reversed-phase C18 column at 50 °C using a mobile phase containing 25% acetonitrile, 45% methanol and 30% ammonium acetate (0.05 M). The pH was adjusted to pH=9 by the addition of ammonia solution (35%, w/w). The samples were detected using a UV detector at 240 nm. The validation study of the method included the effect of temperature, flow rate, ratio of the components of the mobile phase and the pH of the mobile phase on the efficiency of separation. The linear range of Bromazepam and Midazolam was between 0.12 and 0.18 mg/mL, while that of Medazepam was between 0.08 and 0.12 mg/mL. The relative standard deviation for precision was less than 2%. The linearity, selectivity, accuracy and robustness of the developed method showed acceptable values. The method was applied to the analysis of the samples of raw material of the three compounds under study, and the percentage of recoveries was 99.89%±1.06. It was also applied to the analysis of samples of pharmaceutical preparations of those compounds and spiked serum samples. Recoveries from serum samples ranged between 91.5% and 99.0%. The developed method is suitable for quality control of Bromazepam, Medazepam and Midazolam in their mixtures and in pharmaceutical preparations (tablets, capsules, ampoules). It can also be used to determine their concentrations in serum.