Direct stability-indicating method development and validation for analysis of etidronate disodium using a mixed-mode column and charged aerosol detector.

This paper describes the development and validation of a rapid, direct, and stability-indicating method for analysis of etidronate, a bisphosphonate compound without a UV chromophore. A mixed-mode column was used to separate etidronate from its impurities in an 8-min gradient method and a charged aerosol detector (CAD) was used for detection. The developed HPLC method was validated with respect to specificity, linearity, accuracy, precision, sensitivity, and stability. The method can be used for release and stability testing of etidronate and has applicability to other similar bisphosphonate compounds.

Identification of volatile degradants in formulations containing sesame oil using SPME/GC/MS.

Solid-phase microextraction (SPME), in combination with gas chromatography/mass spectrometry (GC/MS), was used to identify an unknown degradant observed during stability studies of a pharmaceutical formulation containing sesame oil. SPME is a solvent-less, rapid, sensitive, and inexpensive extraction method that minimizes sample preparation. SPME combined with GC is a widely used technique in certain fields, such as food, environmental analysis, forensics, and consumer products, but has only rarely been used for the analysis of pharmaceutical formulations. Hexanal, octanal, 2-octenal, 2-decenal, 2-undecenal, and 2,4-decadienal can be detected and identified by GC/MS, but they cannot be detected by LC/MS due to their volatility and low ionization efficiency under atmospheric pressure ionization conditions. Combining the MS data from the GC/MS with LC/DAD data resulted in the identification of the unknown degradant in the formulation as 2,4-decadienal. The presence of this and other aldehydes was attributed to the oxidative degradation of the unsaturated fatty-acid component in vegetable oils.

Simultaneous determination of formic acid and formaldehyde in pharmaceutical excipients using headspace GC/MS.

Formic acid and its esters, as well as formaldehyde, are trace impurities that are often present in pharmaceutical excipients. These trace impurities can potentially react with amino and/or hydroxyl groups in drugs to form significant levels of degradants. To select the appropriate excipients for a stable formulation, a gas chromatography/mass spectrometry (GC/MS) method was developed and validated for the rapid screening of trace amounts of residual formic acid, its esters and formaldehyde in pharmaceutical excipients. Samples were dissolved or dispersed in acidified ethanol to convert formic acid and formaldehyde to ethyl formate and diethoxymethane, respectively. Identification was conducted using a GC/MS system under scan mode and quantified using a selected ion monitoring (SIM) mode. Evaluation of the mass spectra of ethyl formate and diethoxymethane in the samples indicated that the method is specific. The limits of quantitation of the method were 0.5 ppm for formic acid and 0.2 ppm for formaldehyde. The precision of the method was demonstrated by the acceptable R.S.D. (