Purpose: Low molecular weight volatile amines are commonly applied reagents in pharmaceutical industry. They are frequently used as additives in synthesis routes to control reaction rate or improve product yield by altering pH values of reaction environment. Because of their inherent toxicity, volatile amines are required to be effectively purged and their residual levels need to be accurately measured by reliable analytical methods. Chromatographic methods have become the major tools to determine residual amines in different matrix. Although these separation-based approaches provide accurate concentration information of multiple compounds in a short time scale, they normally counter sensitivity issues due to the highly polar nature of amine compounds, which causes noticeable absorption and peak tailing on columns. In this work, a GC-FID method was developed and optimized to simultaneously determine residues of Triethylamine (TEA), Diisopropylamine (DIPA), and 1,1,3,3-Tetramethylguanidine (TMG) in an active pharmaceutical ingredient (API). The control stage of three bases was also studied with the presence of intermediate and API matrix.
The chromatographic system consists of an Agilent 7890 GC equipped with a FID detector and an Agilent G4513A auto sampler. Data acquisition and processing were performed on Thermo Scientific Atlas CDS software. Different GC columns and inlet liners were evaluated in the method development work. The needle in the GC system was rinsed three times with acetonitrile between injections
The mixture of three bases was prepared by quantitatively weighing 100 mg TEA, 70 mg DIEA, and 100 mg TMG into a 100-mL volumetric flask. The mixture was dissolved with acetonitrile to the scale and used as the stock solution. The standard and linearity solutions were prepared by diluting the stock solution to the desired concentrations (0.1 mg/mL for TEA, 0.07 mg/mL for DIEA, and 0.1 mg/mL for TMG in the standard solution). The quantitation limit (QL) solution (0.025 mg/mL for TEA, 0.018 mg/mL for DIEA, and 0.025 mg/mL for TMG) was prepared by serial dilutions of the standard solution. The standard solution is stable under room temperature for at least 3 days. The sample solution was prepared by dissolving 150 mg ABT-620 API with 1 mL of acetonitrile in a 4-mL scintillation vial. The vial was gently shaken to dissolve the API. The sample solution has at least 3 days stability at 2-8 degree storage condition. For recovery study, 1 mL of linearity solution at different concentrations was mixed with 150 mg API, separately.
Haixiao Qiu– Sr. Scientist, AbbVie, Illinois