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The development of a GC method for analysis of resi- dual acetic acid, triethylamine and N,N-dimethylfor- mamide in hydrochloride salts of pharmaceutical substances

Joanna M. Biernat ,  Bożenna A. Kosmacińska 

Instytut Farmaceutyczny (PRI), Rydygiera 8, Warszawa 01-793, Poland

Abstract

Methods for determination of acetic acid, triethylamine and N,N-dimethylformamide as residual solventsin an API hydrochloride by GC method have been developed.

The main issue of the study was to find a solvent, which would guarantee dissolution of hydrochloride of pharmaceutical substances on the one hand, and allow for quantitative determination of acetic acid, triethylamine and N,N-dimethylformamide on the other. The tested substance was insoluble in solvents usually applied for GC analyses as: DMA, DMSO and DMI. After testing a few polar solvents, a mixture: 20% v/v of 25% aq NH4OH in methanol was used.

The residual solvents were determined by direct injection gas chromatography with the use of flame-ionization detector and HP-PlotQ column (30 m long, 0,32 mm ID, 20 µm stationary phase).

Observed peak areas in the chromatograms of the standard working solutions (specification levels of analytes) were smaller than the corresponding peak areas in the chromatograms of the spiked tested substance sample with analytes solution at the same specification levels. That’s why in the GC method the spiked sample with analyzed residual solvents at the specification levels must be used as standard solution.

According to the European Agency for the Evaluation of Medical Products it is considered that the amount of said solvents in pharmaceutical product must not exceed: acetic acid 5 000 ppm and N,N-dimethylformamide 880 ppm. For triethylamine specification limit has been established at the level NMT 0.15% (according to ICH Harmonised Tripartite Guideline – known impurity).

The method was validated and the validation included: selectivity, specificity, system precision, method precision, intermediate precision, accuracy (recovery), linearity, limits of detection and quantitation, robustness.

 

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Related papers

Presentation: Poster at VII Multidyscyplinarna Konferencja Nauki o Leku, by Joanna M. Biernat
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-03-15 09:57
Revised:   2010-04-21 14:42