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.

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/22985 must be provided.

1. Problems of determination of selected Class 1 residual solvents (according to ICH^*)) as process impurities of some Class 3 and 2 solvents in API by GC-HS method
2. Structural characterization of PX-S
3. The determination of chromatografic purity of Pramipexole Dihydrohloride Monohydrate