Simultaneous determination of eight short‐chain aliphatic amines in drug substances by HPLC with diode array detection after derivatization with halonitrobenzenes

Abstract

Short-chain aliphatic amines are a class of hazardous impurities in drug substances. A simple method, involving derivatization followed by high-performance liquid chromatography with diode array detection, has been developed for residue determination of eight aliphatic amines simultaneously in drug substances. Different halonitrobenzenes derivatization reagents were systematically compared. As a result, 1-fluoro-2-nitro-4-(trifluoromethyl)benzene was selected since the derivatization effectively shifted the absorption wavelength to the visible region (400-450 nm), where most drug substances, impurities and even the derivatization reagent absorb very weakly. Due to the redshift effect, interference was minimized and adequately low limits of quantitation were reached (0.24-0.80 nmol/mL). Moreover, the derivatization reaction was readily carried out in dimethyl sulfoxide at room temperature for 1 h using N,N-diisopropylethylamine as catalyst to achieve the highest yield. Without any pre-treatment, the derivatives were analyzed by high-performance liquid chromatography with diode array detection. The high stability of the derivatives within 24 h at room temperature (RSD<1.04%) further facilitated the simultaneous preparation and consecutive analysis of quantities of samples. Finally, the proposed method was successfully applied for residue determination of eight aliphatic amines simultaneously in eight drug substance samples. This study could be helpful for the routine analysis and residue control of aliphatic amines in drug substances.

Determination of dimethylamine and nitrite in pharmaceuticals by ion chromatography to assess the likelihood of nitrosamine formation

“…The LOD of DMA is about 1000 times lower than headspace gas chromatography method (930 μg/L) [ 17 ]. The reported LOD of DMA is 5.4 μg/L by HPLC with diode array detection after derivatization with halonitrobenzenes, and 0.75 μg/L by hydrophilic interaction chromatography coupled with mass spectrometry detection (HILIC-MS) [ 11 , 18 ]. The LOD of DMA using our method is close to HILIC-MS method without the need of a high-cost mass spectrometer.…”

“…Dimethylamine in drug products can be determined by HPLC with fluorescence detection [ 11 ]. The method requires a lengthy derivatization process in order to achieve the highest yield.…”

Application of micro‐solid‐phase extraction for the on‐site extraction of heterocyclic aromatic amines in seawater

“…The selection of a suitable sorbent is crucial as it determines the selectivity of the analytical technique, as each sorbent contains different functional groups and thus have different affinities for the target analytes. C 2 (Si-C 2 H 5 ), C 8 (Si-C 8 Among the silicabased sorbents, C 18 is the most hydrophobic and least polar because of its long hydrocarbon chain. It can retain nonpolar solutes strongly.…”

“…The International Agency for Research on Cancer considers the HAA as possible human carcinogens [6,7]. Analysis of HAA is other challenging task, there are several chromatographic methods such as HPLC-UV [8], fluorometric detection [9], and GC-MS [10] have been used to separate various HAA. GC-MS provides rapid identification and quantification; however, this technique needs a time-consuming and costly derivatization step during extraction.…”

Simultaneous determination of isomeric substituted anilines by imidization with benzaldehyde and gas chromatography–mass spectrometry

“…Determination of these weak organic bases often requires derivatization before GC or LC analysis, due to their liability to peak tailing or little retention in the reversed‐phase LC setup that may deteriorate their resolution. A number of methods have been developed for the derivatization of amines, based on reaction of the amino group, to decrease their polarity or to improve their hydrophobicity, where the corresponding derivatives showed higher extraction efficiency and better chromatographic behavior relative to their precursor amines . Replacement of amino group by iodine has been reported to improve the selectivity and the sensitivity in the determination of aromatic amines by using either electron capture detection , fluorescence detection , or mass spectrometric detection .…”