Determination of Dimethylamine and Triethylamine in Hydrochloride Salts of Drug Substances by Headspace Gas Chromatography using Dimethyl Sulphoxide- imidazole as Diluent

Abstract

A simple, rapid, accurate and precise analytical method for determination of secondary and tertiary amines in hydrochloride salt form of drug substances in non-aqueous medium, which does not require any derivatization, was developed by headspace gas chromatography. Dimethylamine hydrochloride and triethylamine hydrochloride were analyzed in metformin hydrochloride. The sample was dissolved in a vial containing dimethyl sulphoxide and imidazole. The vials were incubated at 100°, for 20 min. The syringe temperature was maintained at 110°. DB624 column with 30 m×0.32 mm i.d., 1.8 µm film thickness was used. The injector and detector temperature were 200° and 250°, respectively. The analytical program used was carrier gas (nitrogen) flow rate: 1 ml/min; injected gas volume: 1.0 ml; split ratio: 1:10; oven temperature program: 40° for 10 min, followed by an increase up to 240° at 40°/min. The analytical method was validated with respect to precision, recovery, limit of detection and quantification and linearity.

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

“…The calculated LOD of DMA was 0.960 and 0.718 μg/L using the CS16 and CS19 columns, respectively. 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 method requires a lengthy derivatization process in order to achieve the highest yield. A headspace gas chromatography (GC) method for DMA determination does not require derivatization [ 12 ]. However, the GC method requires sample preparation to convert the salt form of the amine to the free base.…”

Analytical determination of ethylenediamine impurity in tripelennamine hydrochloride by gas chromatography–mass spectrometry using phthalaldehyde as the derivatizing agent

“…Most pharmaceutical companies utilize the guidelines provided by the European Medicines Agency and the ICH M7(R1) to regulate toxic impurities in drug substances (European Medicines Agency, 2006;ICH Harmonised Guideline, 2017). Following this, further research studies have been conducted to assess the carcinogenic and genotoxic contaminants found in pharmaceutical drug substances using a variety of analytical techniques including HPLC, ultra-performance liquid chromatography, GC, LC-tandem mass spectrometry, and GC-MS. (Babu et al, 2018;Balaji et al, 2022;Balaji & Sultana, 2017;Chen et al, 2020;Chittireddy et al, 2023;Feng et al, 2016;Gopalakrishnan & Devi, 2016;Grace et al, 2019;Kosuri et al, 2023;Lee et al, 2022;Louati et al, 2018;Narapereddy & Alladi, 2023;Nekkala et al, 2017;Neyer et al, 2020;Pandey et al, 2011;Sajan et al, 2015;Siva Jyothi & Venkatnarayana, 2021;Sojitra et al, 2019;Tatipamula et al, 2019;Uppala & Arthanareeswari, 2021;Vijaya Bhaskar Reddy et al, 2014;Wang et al, 2016;Yelampalli et al, 2019).…”

Method Development for the Acquisition of Adsorption Isotherm of Ion Pair Reagents Tributylamine and Triethylamine in Ion Pair Chromatography

“…In contrast to LC, well established GC methods exist for the analysis of alkylamines in different media using modern capillary columns [31][32][33] . However, due to the highly polar and reactive nature of primary, secondary and lower aliphatic tertiary amines, their performance on the routine capillary GC columns is unsatisfactory.…”